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Psoriasis

GtoPdb Disease Summaries

This section gives an overview of the disease, and where available shows the following:

  • Synonyms: Shows known synonyms for the disease.
  • Description: Gives a basic description/definition of the disease.
  • Database Link: External links to the same disease at the Disease Ontology, OMIM or Orphanet sites.
  • Immunopharmacology comments: General comments about the target's role in immunopharmacology, provided by GtoImmuPdb curators.
  • Associated with: Counts are displayed for the total targets the disease is associated with in GtoPdb. The counts of targets and ligands of immunological relevance associated to the disease are also shown.

More information can be found in the help pages.

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Disease ID:801
Name:Psoriasis
Associated with:4 targets
2 immuno-relevant targets
58 immuno-relevant ligands
Description
A long-term autoimmune disease characterized by patches of red, itchy, and scaly skin. Five types of psoriasis are recognised: plaque (psoriasis vulgari), guttate, inverse, pustular, and erythrodermic, with plaque psoriasis being the most common type.
Database Links
Disease Ontology: DOID:8893

Targets

GtoPdb Disease Summaries - Targets

Click on the target name to link to its detailed view page

Where available, information is display on the role of the target in the disease; drugs which target the disease and their therapeutic use and side-effects.

If there is mutation data curated in GtoPdb this is indicated, with a link back to the appropriate section on the target detailed view page

Immuno ligand interactions - If available, a table of immuno-relevant ligands is shown. These ligands have been curated as having an association to the disease and possess interaction data with the target in GtoPdb. The approval status of the ligand is shown, along with curator comments and an indication of whether the target is considered the primary target of the ligand.

More information can be found in the help pages.

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Key to terms and symbols
C5a1 receptor
Role:  Evidence of a role for C5aR in psoriasis stems from the observation that the ligands for C5aR, C5a/C5a-des-arg, are the most abundant cytokine isolated from human psoriatic scales.
References:  5,46
NLRP1
CD2
Comments:  CD2 is the molecular target of alefacept, a drug that was approved for the treatment of moderate to severe plaque psoriasis.
Ligand interactions: 
Ligand Comments
alefacept
Approved drug for plaque psoriasis (no longer authorised for use in some countries).
CD6
Comments:  CD6 is the molecular target of itolizumab, a drug approved for the treatment of chronic plaque psoriasis.
Ligand interactions: 
Ligand Comments
itolizumab
Approved drug for chronic plaque psoriasis.

Ligands

GtoPdb Disease Summaries - Ligands

Click ligand name to view ligand summary page

  • Approved: If the ligand is an approved drug this is indicated, along with approval bodies.
  • Immuno: Immuno icon indicates the ligand is immuno-relevant

Click the arrow in the final column to expand comments

  • Immuno Disease Comments: Curatorial comments specifically added as part of GtoImmuPdb. They give more information on the association between the ligand and disease in the context of immunopharmacology.
  • Clinical Use: General clinical comments relating to the ligand and may not necessarily be specific to the disease in question. With hyperlink to more details on the ligand summary pages.
  • Bioactivty Comments: Curatorial comments specifically about the compounds biological activity - with hyperlink to more details on the ligand summary pages.

More information can be found in the help pages.

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Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
vunakizumab
Immuno Disease Comments: In clinical trial in China.
Clinical Use: Vunakizumab (SHR-1314) has advanced to clinical evaluation in patients with psoriasis. | View clinical data
doramapimod
Immuno Disease Comments: Phase 2 clinical candidate for psoriasis.
Clinical Use: Doramapimod (as research code BIRB 796) has been assessed in Phase 2 clinical trials for plaque-type psoriasis and rheumatoid arthritis (RA). Additional trials for RA and Crohn's disease were terminated. Development of the compound has not progressed beyond Phase 2. | View clinical data
Bioactivity Comments: Doramapimod shows moderate selectivity for the p38α, -β and -γ isozymes compared to p38δ [45]. A Kd value of 0.1nM is reported in [51], but the authors do not specify subtype identity. In a screening panel of kinases, doramapimod inhibited many kinases with IC50 values <100nM (see Supplementary Information attached to [45]). | View biological activity
CXCL11 29
Immuno Disease Comments: CXCL11 (and CCL5) expression is increased in lesional compared with nonlesional psoriatic skin, and levels correlate with levels of IFNγ in the skin samples.
guselkumab
Immuno Disease Comments: First anti-IL-23 biologic therapy to be approved. Approved for the treatment of moderate to severe plaque psoriasis, in patients considered as candidates for systemic therapy or phototherapy.
Clinical Use: Having completed Phase 3 clinical trials for various forms of psoriasis, guselkumab was approved in 2017 for patients with moderate to severe plaque psoriasis. Click here to link to ClinicalTrials.gov's listing of Phase 3 guselkumab trials. | View clinical data
Bioactivity Comments: Results from an earlier clinical trial indicate that 50-100% of guselkumab-treated patients achieved a 75% improvement in psoriasis area severity index scores12 weeks after a single dose treatment. None of the patients receiving placebo showed any improvement [58]. Decreased epidermal thickness and T-cell and dendritic cell expression was observed in lesional and nonlesional skin biopsies from guselkumab-treated patients compared with placebo-treated patients, indicative of improved disease control [58].
Development of guselkumab is claimed in patent US7935344 [4], where it is likely to be the monoclonal identified as 3759EQ/QS, based on peptide sequence identity. The patent provides a graphical representation of 3759EQ/QS displacement of IL-23 binding to IL-23R (in Figure 10), but does not provide a calculated affinity constant or IC50 value for this binding assay. | View biological activity
mirikizumab
Immuno Disease Comments: Phase 2 clinical candidate for moderate to severe plaque type psoriasis- see NCT02899988.
Clinical Use: Mirikizumab (LY3074828) was advanced to Phase 3 evaluation in autoimmune conditions, including psoriasis, ulcerative colitis, Crohn's disease. It was granted first approval in Japan in 2023, as an induction and maintenance treatment for ulcerative colitis [32]. | View clinical data
Bioactivity Comments: Mirikizumab (Antibody I) binds monkey IL-23 with a Kd of 0.056nM, and rabbit IL-23 with a Kd of 53nM, but does not bind rat or mouse IL-23 or human IL-12, IL-27 or IL-35 [3]. Antibody I blocks binding of IL-23 to the IL-23R in vitro, but does not inhibit IL-23 binding to IL-12Rβ1 (the other subunit of the functional IL-23R heterodimer). Effects of Antibody I in vivo are described in the associated patent documentation [3]. | View biological activity
piclidenoson
Immuno Disease Comments: Clinical candidate for plaque psoriasis (Phase 2 NCT00428974).
Clinical Use: Piclidenoson (CF101) is being evaluated in a number of clinical trials, as a potential therapy for several autoimmune-inflammatory disorders (rheumatoid arthritis, Phase 2I, NCT02647762 [65]; plaque psoriasis, Phase 2 [9]; uveitis Phase 2) and glaucoma (Phase 2, NCT01033422 [15]). | View clinical data
GSK2981278 57
Immuno Disease Comments: Phase 2 clinical candidate for plaque type psoriasis (see NCT03004846).
Clinical Use: GSK2981278 has completed Phase 2 clinical trial (NCT03004846) in patients with plaque psoriasis. | View clinical data
Bioactivity Comments: GSK2981278 inhibits activation of the IL17 promoter in a reporter gene assay [57]. Concentrations of GSK2981278 ≥ 3nM leads to almost complete inhibition of IL-17A protein secretion. | View biological activity
CEP-37440
Immuno Disease Comments: Phase 2 clinical candidate for moderate-severe psoriasis- see NCT02931838
Clinical Use: CEP-37440 has completed Phase 1 clinical trial as an oncology candidate (see NCT01922752). | View clinical data
Bioactivity Comments: CEP-37440 inhibits ALK-driven cell proliferation with an IC50 of 22nM, and FAK-driven cells with an IC50 of 82nM [49]. | View biological activity
tapinarof
Immuno Disease Comments: Approved as a treament for plaque psoriasis irrespective of disease severity.
Clinical Use: Topically applied tapinarof (research code GSK2894512) demonstrated clinical efficacy in Phase 2 and Phase 3 clinical trials in patients with plaque psoriasis (PS) [6,40]. Tapinarof has also completed Phase 1 studies for atopic dermatitis. The first FDA approval (May 2022) authorised use of tapinarof (Vtama®) as a treament for PS. Unlike steroid-based anti-inflammatory drugs that are used to treat PS, tapinarof has an unlimited duration of use and can be used on sensitive body areas. | View clinical data
Bioactivity Comments: Tapinarof inhibits proinflammatory cytokine expression in vitro and exhibits anti-inflammatory effects in vivo [56]. | View biological activity
seletalisib 25
Immuno Disease Comments: Phase 1 clinical candidate for psoriasis- see NCT02303509
Clinical Use: First-in-human results were reported by Helmer et al. (2017) [25]. This article reports data from clinical trials NCT02303509 (safety and tolerability in healthy and psoriatic subjects) and NCT02207595 (safety and tolerability in healthy subjects only). A proof of concept Phase 2 trial in patients with primary Sjögren's syndrome has been terminated due to difficulty in enrolling suitable patient numbers (NCT02610543). | View clinical data
fezakinumab
Immuno Disease Comments: Completed Phase 1 trial for psoriasis (see NCT00563524).
Clinical Use: Fezakinumab (ILV-094) has reached Phase 2 for atopic dermatitis (NCT01941537 ongoing), rheumatoid arthritis (NCT00883896 completed) and Phase 1 for psoriasis (NCT00563524 completed). | View clinical data
Bioactivity Comments: Fezakinumab shows cross-species reactivity, blocking IL-22 receptor activation and cellular proliferation induced by murine, monkey and rat IL-22 in addition to the human cytokine [16]. | View biological activity
MK-0873
Immuno Disease Comments: Completed Phase 2 trial for plaque psoriasis- see NCT01140061
Clinical Use: MK-0873 has completed Phase 2 clinical evaluation in rheumatoid arthritis (NCT00132769), and Phase 1 as a topical agent for plaque psoriasis (NCT01235728). A Phase 2 trial in patients with chronic obstructive pulmonary disease (COPD) was terminated (NCT00132730). | View clinical data
Bioactivity Comments: MK-0873 inhibits LPS-induced production of TNF-α in human whole blood assays. Only the IC50 of MK-0873 vs. PDE4A is defined in [22], but the authors state less than a 5-fold difference in the IC50 values across the 4 PDE4 isozymes (4A, 4B, 4C and 4D). | View biological activity
CCL2
Immuno Disease Comments: CCL2 is implicated in the pathogenesis of psoriasis.
cortisol
Immuno Disease Comments: Glucocorticoid drug used to treat many inflammatory condtions including psoriasis.
Clinical Use: Hydrocortisone is used to treat many immune and allergic disorders, adrenal insufficiency disorders (eg Addison's disease), corticosteroid-responsive dermatological disorders (eg psoriasis, atopic dermatitis, and contact dermatitis) and congenital adrenal hyperplasia. | View clinical data
triamcinolone
Immuno Disease Comments: Glucocorticoid drug used to treat many inflammatory condtions including psoriasis.
Clinical Use: Triamcinolone is used for its antiinflammatory or immunosuppressive actions in many conditions. For example, oral triamcinolone is used to treat conditions such as allergic disorders, skin conditions, ulcerative colitis, arthritis, lupus, psoriasis, and breathing disorders. This drug is also used topically as an anti-inflammatory and anti-pruritic agent. Injectable forms of the drug may be used to reduce intra-articular joint pain, stiffness and swelling associated with rheumatoid and osteoarthritic arthritis, bursitis, epicondylitis, and tenosynovitis. | View clinical data
ACTH
Immuno Disease Comments: A corticotropin used to treat the symptoms of many inflammatory disorders including psoriasis.
Clinical Use: Corticotropin is used to treat the symptoms of many allergic disorders, psoriasis and other skin conditions, eye conditions, arthritis, lupus, multiple sclerosis, ulcerative colitis and breathing disorders, for example. This peptide is also used to diagonse adrenocortical insufficiency. | View clinical data
Bioactivity Comments: Although we have recorded affinity data for ACTH at melanocortin receptors 1, 3, 4 and 5, affinity data for the human melanocortin receptor 2, the peptide's primary target, is lacking. As a peptide mimetic of ACTH we would expect corticotropin to have similar affinities to the endogenous peptide. | View biological activity
adalimumab
Immuno Disease Comments: Anti-TNFα monoclonal antibody therapy approved for psoriatic arthritis and plaque psoriasis.
Clinical Use: Used in the management of rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease and plaque psoriasis.
In 2015 both the EMA and the FDA approved the use of adalimumab as a treatment for hidradenitis suppurativa, a chronic skin disease that causes abscesses and scarring on the skin.
In July 2016, the FDA expanded adalimumab approval as the first non-corticosteroid drug available for use as a treatment for non-infectious intermediate, posterior and panuveitis (forms of autoimmune-driven inflammation of the uvea)- results from Phase 3 clinical trial NCT01138657 are published in [26]. The EMA marketing authorisation for adalimumab Trudexa® was withdrawn at the request of the marketing authorisation holder. | View clinical data
IL-17A
Immuno Disease Comments: Approved therapy for psoriasis.
methimazole
Immuno Disease Comments: Approved drug for psoriasis.
Clinical Use: Used in the treatment of hyperthyroidism, goiter, Graves disease and psoriasis. | View clinical data
golimumab
Immuno Disease Comments: An anti-TNFα therapy approved for psoriasis.
Clinical Use: Used in adults with various inflammatory conditions [67] e.g. moderate to severe active rheumatoid arthritis [31], active psoriatic arthritis, active ankylosing spondylitis and moderate to severe ulcerative colitis. | View clinical data
alefacept
Immuno Disease Comments: Approved drug for plaque psoriasis (no longer authorised for use in some countries).
Clinical Use: This drug was approved for the treatment of inflammation in moderate to severe psoriasis with plaque formation. Use of alefacept has since been discontinued in the US. | View clinical data
Bioactivity Comments: The Miller et al. (1993) article does not provide a calculated IC50 value for LFA3TIP's inhibition of the CD2/LFA-3 interaction [44]. The inhibition is assessed by measuring rosetting of Jurkat/human red blood cells (with an approximate IC50 of 1-5μg/ml of protein from graphical data in Figure 3a), or by measuring inhibition of induced T cell proliferation (with LFA3TIP inhibition at approximately 86%) [44]. | View biological activity
efalizumab
Immuno Disease Comments: Approved drug for psoriasis which was later withdrawn from the market.
Clinical Use: Used to treat psoriasis prior to withdrawl from the market. | View clinical data
Bioactivity Comments: A peptide BLAST search using the heavy chain peptide sequence of efalizumab identifies sequence ID 5 in patent US6703018 [27] and data is presented from the monoclonal variant designated MHM24 F(ab)-8. | View biological activity
etanercept
Immuno Disease Comments: Approved drug for severe plaque psoriasis.
Clinical Use: Used to treat severe active rheumatoid arthritis in adults, severe juvenile idiopathic arthritis, ankylosing spondylitis, and severe plaque psoriasis. | View clinical data
ustekinumab
Immuno Disease Comments: An anti-IL-12B therapy approved to treat psoriasis.
Clinical Use: Used to treat adult patients (18 years or older) with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy and is approved in the US to treat psoriatic arthritis. | View clinical data
Bioactivity Comments: The patent covering the production and use of ustekinumab (US6902734 [18]) does not provide affinity values for specific antibody clones, therefore we have included the stated range of affinities determined in the production and testing process in the interaction table below.. | View biological activity
amcinonide
Immuno Disease Comments: A glucocorticoid (corticosteroid) drug used to treat psoriasis.
Clinical Use: Used to treat itching and inflammation associated with allergic and other inflammatory skin conditions. | View clinical data
betamethasone
Immuno Disease Comments: A glucocorticoid (corticosteroid) drug used to treat psoriasis.
Clinical Use: Betamethasone is a synthetic glucocorticoid receptor (GR) agonist, with anti-inflammatory, antipruritic, and vasoconstrictive activities. The drug is used to treat the inflammatory sympotoms of conditions including atopic, seborrhoeic, and contact dermatitis, psoriasis and insect bite reactions. | View clinical data
clobetasol propionate
Immuno Disease Comments: A glucocorticoid (corticosteroid) drug used to treat psoriasis.
Clinical Use: Used to treat skin inflammation and itching caused by conditions such as allergic reactions, eczema, and psoriasis. | View clinical data
desonide
Immuno Disease Comments: A glucocorticoid (corticosteroid) drug used to treat psoriasis.
Clinical Use: Used to reduce skin inflammation caused by allergic reactions, eczema and psoriasis. | View clinical data
Bioactivity Comments: We have been unable to find publicly available affinity data for this drug to substantiate its MMOA, so have not tagged a primary drug target in this case. | View biological activity
desoximetasone
Immuno Disease Comments: A glucocorticoid (corticosteroid) drug used to treat psoriasis.
Clinical Use: Used to reduce skin inflammation caused by allergic reactions, eczema and psoriasis. | View clinical data
diflorasone diacetate
Immuno Disease Comments: A glucocorticoid (corticosteroid) drug used to treat psoriasis.
Clinical Use: Used to reduce skin inflammation caused by allergic reactions, eczema and psoriasis. | View clinical data
flumethasone pivalate
Immuno Disease Comments: A glucocorticoid (corticosteroid) drug used to treat psoriasis.
Clinical Use: Used to reduce skin inflammation caused by allergic reactions, eczema and psoriasis. However, there is no information regarding approval for clinical use of this drug on the US FDA website. Other national approval agencies may have granted marketing authorisation. | View clinical data
brodalumab
Immuno Disease Comments: Approved therapeutic for plaque psoriasis.
Clinical Use: Brodalumab was first approved in Japan (2016), and by the US FDA for plaque psoriasis the following year. Regulatory decisions are pending elsewhere. Clinical trials for the treatment of psoriatic arthritis (Phase 2I), moderate to severe plaque psoriasis (Phase 2I) and asthma (Phase 2) are ongoing. Encouraging results from a Phase 2 study have been reported [42]. | View clinical data
Bioactivity Comments: BLAST searches using the peptide sequences of the heavy and light chains of brodalumab link to patent US7767206 [63], and monoclonal antibody clone AMH14/AML14. | View biological activity
ixekizumab
Immuno Disease Comments: Approved therapeutic for psoriasis and plaque psoriasis.
Clinical Use: Ixekizumab is approved for the treatment of psoriasis. Positive results from a Phase 2 study are reported in [17], and Phase 3 results are reviewed in [12]. In March 2016, the US FDA approved ixekizumab for the treatment of moderate-to-severe plaque psoriasis. The EMA granted marketing authorisation in April 2016.
Phase 3 results following 60 weeks of treatment are reported in [19], showing longer term efficacy (with ~80% of patients seeing at least a 75% improvement in their skin symptoms at 60 weeks). | View clinical data
prednicarbate
Immuno Disease Comments: A glucocorticoid (corticosteroid) drug used to treat psoriasis.
Clinical Use: Prednicarbate is a topical corticosteroid drug [23]. It is used to relieve inflammatory and pruritic symptoms of corticosteroid-responsive skin conditions such as seborrheic or atopic dermatitis, localized neurodermatitis, psoriasis, the late phase of allergic contact dermatitis and the inflammatory phase of xerosis cutis. Prednicarbate is claimed to have low atrophogenic potential compared to other glucocorticoids [33,36]. | View clinical data
Bioactivity Comments: We have been unable to find publicly available affinity data for this drug at its proposed molecular target to substantiate its MMOA, and have therefore not tagged a primary drug target. | View biological activity
E6201
Immuno Disease Comments: Phase 2 clinical trial for Psoriasis vulgaris has been completed. More recently, a Phase 1/2 study in FLT3 mutation positive AML has been initiated (NCT02418000).
Clinical Use: E6201 has been assessed in the completed clinical trial NCT01268527 (Phase 2), for the treatment of psoriasis vulgaris. As of October 2018 there is only one active E6201 clinical trial registered with ClinicalTrials.gov, NCT03332589 (Phase 1), which will evaluate efficacy in metastatic melanoma patients. | View clinical data
Bioactivity Comments: E6201 has significant inhibitory effects on pro-inflammatory cytokine production from various immune cells, and inhibits hyperproliferation of human keratinocytes [21,47,54], activities which underscore its potential as a drug candidate for the treatment of psoriasis. The compound also has potential antineoplastic activity. | View biological activity
sotrastaurin
Immuno Disease Comments: Completed Phase 2 clinical trial NCT00885196 for plaque psoriasis.
Clinical Use: Sotrastaurin (AEB071) has been assessed in a number of clinical trials, for a wide variety of oncology indications, in autoimmune conditions such as plaque psoriasis, and also as an anti-rejection therapy following kidney/liver transplantation. Link here to ClinicalTrials.gov's listing of currently registered sotrastaurin trials. The only open trial (May 2017) is Phase 1 NCT02273219 in uveal melanoma. | View clinical data
secukinumab
Immuno Disease Comments: Approved therapeutic for plaque psoriasis.
Clinical Use: Secukinumab is approved by the US FDA for the treatment of plaque psoriasis.
Secukinumab also met its clinical endpoints in Phase 2I clinical trial for ankylosing spondylitis (NCT01649375) [2], and was FDA approved for this indication and psoriatic arthritis [41,43] in January 2016.
The antibody is also in Phase 2 clinical trial for multiple sclerosis (NCT01874340) based on results from experiments in an animal model of the disease (experimental autoimmune encephalomyelitis, EAE) and in vitro human cell assays [11]. | View clinical data
tildrakizumab 52
Immuno Disease Comments: Approved drug for moderate to severe plaque psoriasis.
Clinical Use: Tildrakizumab completed Phase 3 clinical trial for plaque psoriasis (NCT01729754 and NCT01722331), and having shown significant clinical benefit over placebo and and a favourable safety profile [52], was EMA and FDA approved in 2018, for the treatment of phototherapy candidate, adult patients with moderate to severe plaque psoriasis. | View clinical data
itacitinib
Immuno Disease Comments: Phase 2 study NCT01634087 in psoriasis has been completed.
Clinical Use: INCB039110 is being assessed in Phase 2 clinical trials as a potential treatment for indications such as rheumatoid arthritis (RA), post essential thrombocythemia myelofibrosis, chronic plaque psoriasis and non-small cell lung cancer (NSCLC). Phase 3 trials in chronic graft-versus-host disease are also underway. Click here to link to ClinicalTrials.gov's complete list of INCB039110 studies. | View clinical data
navarixin
Immuno Disease Comments: Completed Phase 2 clinical trial NCT00684593 for psoriasis.
Clinical Use: Navarixin (SCH-527123) has been evaluated in a number of Phase 2 clinical trials for immune conditions such as allergen-induced asthma, chronic obstructive pulmonary disease (COPD) and psoriasis. Development for these indications appears to have been discontinued. As of January 2019 the only active trial involving navarixin is NCT03473925, a Phase 2 study looking for efficacy of navarixin plus in a selected range of advanced/metastatic solid tumours. | View clinical data
adriforant
Immuno Disease Comments: Completed Phase 2 trial in psoriasis (see NCT02618616).
Clinical Use: ZPL-3893787 reached Phase 2 clinical trial for evaluation as an antiinflammatory agent in patients with plaque psoriasis (see NCT02618616), and a Phase 1 in atopic dermatitis has been completed. Although the compound was better than placebo at reducing eczema symptoms such as inflammation in a phase 2a study for moderate-severe atopic dermatitis, it failed to meet an itch-related endpoint. Novartis terminated their ZPL-3893787 programme in mid-2020. | View clinical data
bimosiamose
Immuno Disease Comments: No progress beyond Phase 2 trial.
Clinical Use: Bimosiamose has completed Phase 2 clinical trials in patients with chronic obstructive pulmonary disease (COPD; inhaled bimosiamose, NCT01108913 [66]) and psoriasis (topically applied bimosiamose, NCT00823693) | View clinical data
Bioactivity Comments: We do not include the selectins as molecular targets in this database.
Bimosiamose (TBC1269) has a reported IC50 of 70μM in a P-selectin HL-60 cell assay [35]. | View biological activity
timolumab
Immuno Disease Comments: Completed Phase 1 clinical trial NCT00871598.
Clinical Use: Timolumab (with research code BTT1023) is being evaluated in Phase 2 clinical trial NCT02239211, for its potential to treat patients with primary sclerosing cholangitis, an uncommon and progressive disease of the bile ducts characterised by inflammation and obliterative fibrosis. Phase 1 studies for RA and psoriasis have been completed (2010/11). | View clinical data
risankizumab
Immuno Disease Comments: Approved therapy for moderate to severe psoriasis (FDA April 2019).
Clinical Use: Results from the first-in-human proof-of-concept trial in patients with psoriasis were reported by Krueger et al. in 2015 [38]. Phase 3 trial results in psoriasis patients were published in 2018 [20]. FDA and EMA approvals were granted in 2019 and it is also approved in Japan and Canada. Risankizumab therapy is indicated for patients with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy (Japan's authorisation additionally includes treatment of generalized pustular psoriasis, erythrodermic psoriasis and psoriatic arthritis). Investigations are ongoing in other autoinflammatory conditions. Click here to link to ClinicalTrials.gov's full list of risankizumab trials.

In May 2022, two studies reported results from phase 3 RCTs of risankizumab for Crohn's disease [8,14]. The NCT04524611 (SEQUENCE) study is directly comparing risankizumab and ustekinumab in participants with moderate to severe Crohn's disease and for whom anti-TNF therapy has failed. | View clinical data
crisaborole
Immuno Disease Comments: Phase 2 clinical candidate for plaque psoriasis.
Clinical Use: Crisaborole (with research code AN2728) has completed Phase 3 clinical trials as a monotherapy for atopic dermatitis (NCT02118792 and NCT02118766) and has received FDA approval for treatment of mild-to-moderate atopic dermatitis in December 2016. | View clinical data
Bioactivity Comments: Inhibits partially purified human PDE4 with an IC50 of 490nM, and inhibits cytokine release in vitro and in vivo [1]. | View biological activity
toreforant
Immuno Disease Comments: No progress beyond Phase 2 trial.
Clinical Use: Toreforant failed to show clinical efficacy in a Phase 2 clinical trial in patients with active rheumatoid arthritis [62]. Phase 2 studies NCT01823016 and NCT02295865 in patients with uncontrolled, persistent asthma and moderate to severe plaque-type psoriasis respectively have been completed. | View clinical data
brazikumab
Immuno Disease Comments: No progress beyond Phase 1 trial.
Clinical Use: Phase 1 clinical trials evaluating brazikumab as a monotherapy in mild to severe Crohn's disease (NCT01258205) and moderate to severe psoriasis (NCT01094093) have been completed. Phase 2 trials in subjects with active, moderate to severe Crohn's disease are ongoing (see NCT02574637 and NCT01714726). | View clinical data
Bioactivity Comments: It is unclear which anti-IL-23 antibody in patent WO2011056600 is AMG 139, although antibodies B and E were crystalised to produce X-ray structures, suggesting these were preferred agents [64]. In binding affinity experiments using recombinant human IL-23, all of the chosen antibodies produced equilibrium dissociation constant (KD) values <4pM [64]. | View biological activity
amiselimod
Immuno Disease Comments: Phase 2 clinical candidate for plaque psoriasis.
Clinical Use: Amiselimod (MT-1303) has completed Phase 2 dose-finding clinical trials in patients with relapsing-remitting multiple sclerosis (NCT01742052) and moderate to severe chronic plaque psoriasis (NCT01987843). Phase 2 trials in Crohn's disease patients are underway. | View clinical data
Bioactivity Comments: In vivo (in mice) amiselimod (MT-1303) hydrochloride decreases peripheral blood lymphocyte count with an ED50 value of 0.04mg/kg body weight [34]. Affinity for S1P receptors is not provided in the patent. Note that bioactivity is attributed to the active metabolite [60], the prodrug is almost completely inactive at S1P1R. | View biological activity
itolizumab
Immuno Disease Comments: Approved drug for chronic plaque psoriasis.
Clinical Use: Itolizumab has been licensed India since 2013 as a treatmant for chronic plaque psoriasis [10,28,39]. Itolizumab has also been evaluated in patients with rheumatoid arthritis [53]. | View clinical data
GSK2982772
Immuno Disease Comments: Clinical candidate in psoriasis.
Clinical Use: GSK2982772 is in Phase 2 clinical trials in psoriasis (NCT02776033), rheumatoid arthritis (NCT02858492), and ulcerative colitis (NCT02903966). | View clinical data
Bioactivity Comments: In a screening panel 10μM GSK2982772 did not inhibit any of the 339 kinases tested by >50% (a level assessed as being inactive). GSK2982772 prevented TNF-induced necrotic cell death, and was effective in an ulcerative colitis explant assay for blocking spontaneous cytokine release [24]. | View biological activity
belumosudil
Immuno Disease Comments: Phase 2 clinical candidate for moderate to severe plaque psoriasis (NCT02852967).
Clinical Use: Belumosudil (KD025) was evaluated in clinical studies for immunosuppressive, anti-inflammatory and anti-fibrotic efficacy. The FDA approved belumosudil (Rezurock®) in July 2021, as a treatment for chronic graft-versus-host disease that has failed to be controlled by at least two prior lines of systemic therapy. | View clinical data
PF-06263276
Immuno Disease Comments: Completed Phase 1 trial in plaque psoriasis patients (see NCT02193815)
Clinical Use: PF-06263276 was progressed to clinical trial and has completed Phase 1 evaluation in subjects with plaque psoriasis (NCT02193815), although this was only a 12 day study. | View clinical data
Bioactivity Comments: In vitro and in vivo potencies, and the pharmacokinetic and safety profiles of PF-06263276 indicate suitability for inhaled or topical therapy to treat inflammatory diseases, such as COPD or psoriasis, through direct administration to the lungs or skin, thus avoiding any systemic effects of JAK inhibition [30]. IC50 evaluation was performed at 100nM ATP. | View biological activity
metformin
Immuno Disease Comments: Clinical trial NCT02644954 was designed to test for efficacy of adjunct metformin in patients with moderate chronic plaque psoriasis, however it is unclear if this trial was ever initiated.
Clinical Use: Used in the management of non-insulin dependent type 2 diabetes as an adjunct to diet and exercise. Also used in the management of polycystic ovary syndrome (PCOS).
Metformin is combined with in Invokamet®, (also marketed as Vokanamet®) the first fixed-dose combination of an SGLT2 inhibitor with metformin to be approved (by the US FDA, 2014). Later in 2014, the US FDA approved a second SGLT2/metformin drug, Xigduo XR®, which contains (as dapagliflozin propanediol monohydrate PubChem CID 56841155) and metformin hydrochloride. The first approval of a metformin-containing drug mixture by the EMA was for Avandamet (rosiglitazone plus metformin), although this drug was later withdrawn from the market. Avandamet has been superceeded by newer and more effective anti-diabetes combination drugs. | View clinical data
Bioactivity Comments: As the molecular mechanism of metformin is incompletely understood we have not tagged a primary drug target. | View biological activity
galectin-3
Immuno Disease Comments: Experiments in mouse models shows that galectin 3 deficiency contributes to the development of psoriasis-like inflammatory skin lesions. Notably galectin 3 expression is down-regulated in lesional skin from psoriasis patients, but not in their non-lesional skin.
Clinical Use: GB1211 has entered phase 1 safety and tolerability evaluation. | View clinical data
certolizumab pegol
Immuno Disease Comments: Approved drug for moderate-to-severe plaque psoriasis (FDA 2018) and psoriatic arthritis (EMA 2009).
Clinical Use: Used to treat rheumatoid arthritis (RA) and Crohn's disease [7]. May also have some effect in related conditions such as axial spondyloarthritis [59]. The EMA granted Europe-wide approval for the use of this drug in patients with RA (moderate to severe, active disease and severe, active and progressive disease), axial spondyloarthritis and psoriatic arthritis in 2009. FDA approval was expanded to include treatment of moderate-to-severe plaque psoriasis, in June 2018. | View clinical data
Bioactivity Comments: Certolizumab pegol neutralises soluble TNFα in vitro, with an IC90 of 3ng/ml [48], neutralises the effects mediated by membrane bound TNFα, and inhibits production of IL-1β in monocytes stimulated with LPS. | View biological activity
AbGn-168H
Immuno Disease Comments: Phase 2 clinical evaluation of AbGn-168H in patients with moderate to severe chronic plaque psoriasis (NCT01855880) and active psoriatic arthritis (NCT02267642) has been completed, but results have not yet been published (July 2018).
Clinical Use: AbGn-168H has completed Phase 2 clinical evaluation in patients with moderate to severe chronic plaque psoriasis (NCT01855880) and active psoriatic arthritis (NCT02267642). A Phase 2 study in patients with moderate to severe active, anti-TNFα and/or anti-integrin refractory ulcerative colitis has been initiated (NCT03298022), as has a Phase 1 study for steroid-refractory acute graft-versus-host disease (GvHD; NCT03327857). FDA orphan drug designation for the treatment of acute GvHD was granted in January 2018 [13]. | View clinical data
namilumab 50
Immuno Disease Comments: Phase 2 evaluation of namilumab therapy in patients with plaque type psoriasis determined that GM-CSF blockade was not an amenable pathway for treatment of this condition.
Clinical Use: Phase 2 evaluation in a 12 week study has demonstrated the clinical efficacy effected by inhibiting macrophage activity via targeting of GM-CSF in patients with rheumatoid arthritis [61]. | View clinical data
Bioactivity Comments: Namilumab does not bind to either of the other colony-stimulating factors (G-CSF or M-CSF) [37]. It potently neutralises recombinant human GM-CSF produced in E. coli and yeast expression systems, and endogenous GM-CSF from human bronchial epithelial cells. It also binds and neutralises macaque GM-CSF. | View biological activity
COVA322
Immuno Disease Comments: Failed Phase 1 clinical lead for plaque psoriasis. Concerns about COVA322's safety profile led to development being discontinued.
Clinical Use: COVA322 was advanced to Phase 1a/2b clinical evaluation in patients with stable chronic moderate-to-severe plaque psoriasis. The agent was found to be unsafe and the trial was terminated. | View clinical data
Bioactivity Comments: COVA322 binds cynomolgus TNF and IL-17A with affinities of 63 pM and 120 pM respectively [55]. | View biological activity

References

Show »

1. Akama T, Baker SJ, Zhang YK, Hernandez V, Zhou H, Sanders V, Freund Y, Kimura R, Maples KR, Plattner JJ. (2009) Discovery and structure-activity study of a novel benzoxaborole anti-inflammatory agent (AN2728) for the potential topical treatment of psoriasis and atopic dermatitis. Bioorg Med Chem Lett, 19 (8): 2129-32. [PMID:19303290]

2. Baeten D, Sieper J, Braun J, Baraliakos X, Dougados M, Emery P, Deodhar A, Porter B, Martin R, Andersson M et al.. (2015) Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis. N Engl J Med, 373 (26): 2534-48. [PMID:26699169]

3. Beidler CB, Bright SW, Girard DS, Kikly KK. (2015) Antibodies that bind to IL-23. Patent number: US9023358B2. Assignee: Eli Lilly and Co Ltd (GB). Priority date: 08/03/2013. Publication date: 05/05/2015.

4. Benson J, Carton J, Mark Cunningham M, Orlovsky YI, Rauchenberger R, Sweet R. (2011) Human anti-IL-23 antibodies, compositions, methods and uses. Patent number: US7935344. Assignee: Centocor Ortho Biotech Inc.. Priority date: 29/12/2005. Publication date: 01/05/2011.

5. Bergh K, Iversen OJ, Lysvand H. (1993) Surprisingly high levels of anaphylatoxin C5a des Arg are extractable from psoriatic scales. Arch Dermatol Res, 285 (3): 131-4. [PMID:8503693]

6. Bissonnette R, Bolduc C, Maari C, Nigen S, Webster JM, Tang L, Lyle M. (2012) Efficacy and safety of topical WBI-1001 in patients with mild to moderate psoriasis: results from a randomized double-blind placebo-controlled, phase II trial. J Eur Acad Dermatol Venereol, 26 (12): 1516-21. [PMID:22077962]

7. Choy EH, Hazleman B, Smith M, Moss K, Lisi L, Scott DG, Patel J, Sopwith M, Isenberg DA. (2002) Efficacy of a novel PEGylated humanized anti-TNF fragment (CDP870) in patients with rheumatoid arthritis: a phase II double-blinded, randomized, dose-escalating trial. Rheumatology (Oxford), 41 (10): 1133-7. [PMID:12364632]

8. D'Haens G, Panaccione R, Baert F, Bossuyt P, Colombel J-F, Danese S, Dubinsky M, Feagan BG, Hisamatsu T, Lim A et al.. (2022) Risankizumab as induction therapy for Crohn's disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. The Lancet, 399 (10340): 2015-2030. DOI: 10.1016/S0140-6736(22)00467-6

9. David M, Akerman L, Ziv M, Kadurina M, Gospodinov D, Pavlotsky F, Yankova R, Kouzeva V, Ramon M, Silverman MH et al.. (2012) Treatment of plaque-type psoriasis with oral CF101: data from an exploratory randomized phase 2 clinical trial. J Eur Acad Dermatol Venereol, 26 (3): 361-7. [PMID:21504485]

10. Dogra S, D S K, Budamakuntla L, Srinivas CR, Khopkar U, Gupta S, Shetty N, Pratap DV, Gopal MG, Rao TN et al.. (2015) Long-term efficacy and safety of itolizumab in patients with moderate-to-severe chronic plaque psoriasis: A double-blind, randomized-withdrawal, placebo-controlled study. J Am Acad Dermatol, 73 (2): 331-3.e1. [PMID:26183983]

11. Elain G, Jeanneau K, Rutkowska A, Mir AK, Dev KK. (2014) The selective anti-IL17A monoclonal antibody secukinumab (AIN457) attenuates IL17A-induced levels of IL6 in human astrocytes. Glia, 62 (5): 725-35. [PMID:24677511]

12. Farahnik B, Beroukhim K, Zhu TH, Abrouk M, Nakamura M, Singh R, Lee K, Bhutani T, Koo J. (2016) Ixekizumab for the Treatment of Psoriasis: A Review of Phase III Trials. Dermatol Ther (Heidelb), 6 (1): 25-37. [PMID:26910853]

13. FDA. neihulizumab. Accessed on 02/07/2018. Modified on 02/07/2018. US FDA: Orphan Drug Designations and Approvals, https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=622617

14. Ferrante M, Panaccione R, Baert F, Bossuyt P, Colombel J-F, Danese S, Dubinsky M, Feagan BG, Hisamatsu T, Lim A et al.. (2022) Risankizumab as maintenance therapy for moderately to severely active Crohn's disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. The Lancet, 399 (10340): 2031-2046. DOI: 10.1016/S0140-6736(22)00466-4

15. Fishman P, Cohen S, Bar-Yehuda S. (2013) Targeting the A3 adenosine receptor for glaucoma treatment (review). Mol Med Rep, 7 (6): 1723-5. [PMID:23563604]

16. Fouser LA, Hegen M, Luxenberg DP, O'Toole M. (2010) Methods of using antibodies against human IL-22. Patent number: US7811567. Assignee: Wyeth Llc. Priority date: 21/02/2006. Publication date: 12/10/2010.

17. Genovese MC, Greenwald M, Cho CS, Berman A, Jin L, Cameron GS, Benichou O, Xie L, Braun D, Berclaz PY et al.. (2014) A phase II randomized study of subcutaneous ixekizumab, an anti-interleukin-17 monoclonal antibody, in rheumatoid arthritis patients who were naive to biologic agents or had an inadequate response to tumor necrosis factor inhibitors. Arthritis Rheumatol, 66 (7): 1693-704. [PMID:24623718]

18. Giles-Komar J, Knight DM, Peritt D, Scallon B, Shealy D. (2005) Also an IL-12 anti-idiotype antibody to the antibody. Patent number: US6902734. Assignee: Centocor, Inc.. Priority date: 07/08/2000. Publication date: 07/06/2005.

19. Gordon KB, Blauvelt A, Papp KA, Langley RG, Luger T, Ohtsuki M, Reich K, Amato D, Ball SG, Braun DK et al.. (2016) Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis. N Engl J Med, 375 (4): 345-56. [PMID:27299809]

20. Gordon KB, Strober B, Lebwohl M, Augustin M, Blauvelt A, Poulin Y, Papp KA, Sofen H, Puig L, Foley P et al.. (2018) Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. Lancet, 392 (10148): 650-661. [PMID:30097359]

21. Goto M, Chow J, Muramoto K, Chiba K, Yamamoto S, Fujita M, Obaishi H, Tai K, Mizui Y, Tanaka I et al.. (2009) E6201 [(3S,4R,5Z,8S,9S,11E)-14-(ethylamino)-8, 9,16-trihydroxy-3,4-dimethyl-3,4,9,19-tetrahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione], a novel kinase inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-1 and MEK kinase-1: in vitro characterization of its anti-inflammatory and antihyperproliferative activities. J Pharmacol Exp Ther, 331 (2): 485-95. [PMID:19684251]

22. Guay D, Boulet L, Friesen RW, Girard M, Hamel P, Huang Z, Laliberté F, Laliberté S, Mancini JA, Muise E et al.. (2008) Optimization and structure-activity relationship of a series of 1-phenyl-1,8-naphthyridin-4-one-3-carboxamides: identification of MK-0873, a potent and effective PDE4 inhibitor. Bioorg Med Chem Lett, 18 (20): 5554-8. [PMID:18835163]

23. Gupta AK, Chow M. (2004) A review of prednicarbate (Dermatop). Skin Therapy Lett, 9 (10): 5-6, 9. [PMID:15657633]

24. Harris PA, Berger SB, Jeong JU, Nagilla R, Bandyopadhyay D, Campobasso N, Capriotti CA, Cox JA, Dare L, Dong X et al.. (2017) Discovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases. J Med Chem, 60 (4): 1247-1261. [PMID:28151659]

25. Helmer E, Watling M, Jones E, Tytgat D, Jones M, Allen R, Payne A, Koch A, Healy E. (2017) First-in-human studies of seletalisib, an orally bioavailable small-molecule PI3Kδ inhibitor for the treatment of immune and inflammatory diseases. Eur J Clin Pharmacol, 73 (5): 581-591. [PMID:28160012]

26. Jaffe GJ, Dick AD, Brézin AP, Nguyen QD, Thorne JE, Kestelyn P, Barisani-Asenbauer T, Franco P, Heiligenhaus A, Scales D et al.. (2016) Adalimumab in Patients with Active Noninfectious Uveitis. N Engl J Med, 375 (10): 932-43. [PMID:27602665]

27. Jardieu PM, Presta LG. (2004) Method of treatment using humanized anti-CD11a antibodies. Patent number: US6703018. Assignee: Genentech, Inc.. Priority date: 27/11/1996. Publication date: 19/03/2004.

28. Jayaraman K. (2013) Biocon's first-in-class anti-CD6 mAb reaches the market. Nat Biotechnol, 31 (12): 1062-3. [PMID:24316625]

29. Johansen C, Rittig AH, Mose M, Bertelsen T, Weimar I, Nielsen J, Andersen T, Rasmussen TK, Deleuran B, Iversen L. (2017) STAT2 is involved in the pathogenesis of psoriasis by promoting CXCL11 and CCL5 production by keratinocytes. PLoS ONE, 12 (5): e0176994. [PMID:28472186]

30. Jones P, Storer RI, Sabnis YA, Wakenhut FM, Whitlock GA, England KS, Mukaiyama T, Dehnhardt CM, Coe JW, Kortum SW et al.. (2017) Design and Synthesis of a Pan-Janus Kinase Inhibitor Clinical Candidate (PF-06263276) Suitable for Inhaled and Topical Delivery for the Treatment of Inflammatory Diseases of the Lungs and Skin. J Med Chem, 60 (2): 767-786. [PMID:27983835]

31. Kay J, Matteson EL, Dasgupta B, Nash P, Durez P, Hall S, Hsia EC, Han J, Wagner C, Xu Z et al.. (2008) Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate: a randomized, double-blind, placebo-controlled, dose-ranging study. Arthritis Rheum, 58 (4): 964-75. [PMID:18383539]

32. Keam SJ. (2023) Mirikizumab: First Approval. Drugs, 83 (11): 1045-1052. [PMID:37389706]

33. Kerscher MJ, Korting HC. (1992) Topical glucocorticoids of the non-fluorinated double-ester type. Lack of atrophogenicity in normal skin as assessed by high-frequency ultrasound. Acta Derm Venereol, 72 (3): 214-6. [PMID:1357864]

34. Kiuchi M, Marukawa K, Kobayashi N, Sugahara K. (2009) Amine Compound and Use Thereof for Medical Purposes. Patent number: US20090137530. Assignee: Mitsubishi Tanabe Pharma Corporation. Priority date: 15/12/2005. Publication date: 28/05/2009.

35. Kogan TP, Dupré B, Bui H, McAbee KL, Kassir JM, Scott IL, Hu X, Vanderslice P, Beck PJ, Dixon RA. (1998) Novel synthetic inhibitors of selectin-mediated cell adhesion: synthesis of 1,6-bis[3-(3-carboxymethylphenyl)-4-(2-alpha-D- mannopyranosyloxy)phenyl]hexane (TBC1269). J Med Chem, 41 (7): 1099-111. [PMID:9544210]

36. Korting HC, Vieluf D, Kerscher M. (1992) 0.25% prednicarbate cream and the corresponding vehicle induce less skin atrophy than 0.1% betamethasone-17-valerate cream and 0.05% clobetasol-17-propionate cream. Eur J Clin Pharmacol, 42 (2): 159-61. [PMID:1618247]

37. Krinner EM, Raum T, Petsch S, Bruckmaier S, Schuster I, Petersen L, Cierpka R, Abebe D, Mølhøj M, Wolf A et al.. (2007) A human monoclonal IgG1 potently neutralizing the pro-inflammatory cytokine GM-CSF. Mol Immunol, 44 (5): 916-25. [PMID:16697465]

38. Krueger JG, Ferris LK, Menter A, Wagner F, White A, Visvanathan S, Lalovic B, Aslanyan S, Wang EE, Hall D et al.. (2015) Anti-IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol, 136 (1): 116-124.e7. [PMID:25769911]

39. Krupashankar DS, Dogra S, Kura M, Saraswat A, Budamakuntla L, Sumathy TK, Shah R, Gopal MG, Narayana Rao T, Srinivas CR et al.. (2014) Efficacy and safety of itolizumab, a novel anti-CD6 monoclonal antibody, in patients with moderate to severe chronic plaque psoriasis: results of a double-blind, randomized, placebo-controlled, phase-III study. J Am Acad Dermatol, 71 (3): 484-92. [PMID:24703722]

40. Lebwohl MG, Stein Gold L, Strober B, Papp KA, Armstrong AW, Bagel J, Kircik L, Ehst B, Hong HC, Soung J et al.. (2021) Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis. N Engl J Med, 385 (24): 2219-2229. [PMID:34879448]

41. McInnes IB, Mease PJ, Kirkham B, Kavanaugh A, Ritchlin CT, Rahman P, van der Heijde D, Landewé R, Conaghan PG, Gottlieb AB et al.. (2015) Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 386 (9999): 1137-46. [PMID:26135703]

42. Mease PJ, Genovese MC, Greenwald MW, Ritchlin CT, Beaulieu AD, Deodhar A, Newmark R, Feng J, Erondu N, Nirula A. (2014) Brodalumab, an Anti-IL17RA Monoclonal Antibody, in Psoriatic Arthritis. N Engl J Med, 370 (24): 2295-2306. [PMID:24918373]

43. Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P, van der Heijde D, Landewé R, Nash P, Pricop L, Yuan J et al.. (2015) Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis. N Engl J Med, 373 (14): 1329-39. [PMID:26422723]

44. Miller GT, Hochman PS, Meier W, Tizard R, Bixler SA, Rosa MD, Wallner BP. (1993) Specific interaction of lymphocyte function-associated antigen 3 with CD2 can inhibit T cell responses. J Exp Med, 178 (1): 211-22. [PMID:7686212]

45. Moffett K, Konteatis Z, Nguyen D, Shetty R, Ludington J, Fujimoto T, Lee KJ, Chai X, Namboodiri H, Karpusas M et al.. (2011) Discovery of a novel class of non-ATP site DFG-out state p38 inhibitors utilizing computationally assisted virtual fragment-based drug design (vFBDD). Bioorg Med Chem Lett, 21 (23): 7155-65. [PMID:22014550]

46. Mrowietz U, Koch WA, Zhu K, Wiedow O, Bartels J, Christophers E, Schröder JM. (2001) Psoriasis scales contain C5a as the predominant chemotaxin for monocyte-derived dendritic cells. Exp Dermatol, 10 (4): 238-45. [PMID:11493312]

47. Muramoto K, Goto M, Inoue Y, Ishii N, Chiba K, Kuboi Y, Omae T, Wang YJ, Gusovsky F, Shirota H. (2010) E6201, a novel kinase inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-1 and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase-1: in vivo effects on cutaneous inflammatory responses by topical administration. J Pharmacol Exp Ther, 335 (1): 23-31. [PMID:20627998]

48. Nesbitt A, Fossati G, Bergin M, Stephens P, Stephens S, Foulkes R, Brown D, Robinson M, Bourne T. (2007) Mechanism of action of certolizumab pegol (CDP870): in vitro comparison with other anti-tumor necrosis factor alpha agents. Inflamm Bowel Dis, 13 (11): 1323-32. [PMID:17636564]

49. Ott GR, Cheng M, Learn KS, Wagner J, Gingrich DE, Lisko JG, Curry M, Mesaros EF, Ghose AK, Quail MR et al.. (2016) Discovery of Clinical Candidate CEP-37440, a Selective Inhibitor of Focal Adhesion Kinase (FAK) and Anaplastic Lymphoma Kinase (ALK). J Med Chem, 59 (16): 7478-96. [PMID:27527804]

50. Papp KA, Gooderham M, Jenkins R, Vender R, Szepietowski JC, Wagner T, Hunt B, Souberbielle B, NEPTUNE investigators. (2019) Granulocyte-macrophage colony-stimulating factor (GM-CSF) as a therapeutic target in psoriasis: randomized, controlled investigation using namilumab, a specific human anti-GM-CSF monoclonal antibody. Br J Dermatol, 180 (6): 1352-1360. [PMID:30207587]

51. Pargellis C, Tong L, Churchill L, Cirillo PF, Gilmore T, Graham AG, Grob PM, Hickey ER, Moss N, Pav S et al.. (2002) Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site. Nat Struct Biol, 9 (4): 268-72. [PMID:11896401]

52. Reich K, Papp KA, Blauvelt A, Tyring SK, Sinclair R, Thaçi D, Nograles K, Mehta A, Cichanowitz N, Li Q et al.. (2017) Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials. Lancet, 390 (10091): 276-288. [PMID:28596043]

53. Rodriguez PC, Torres-Moya R, Reyes G, Molinero C, Prada D, Lopez AM, Hernandez IM, Hernandez MV, Martinez JP, Hernandez X et al.. (2012) A clinical exploratory study with itolizumab, an anti-CD6 monoclonal antibody, in patients with rheumatoid arthritis. Results Immunol, 2: 204-11. [PMID:24371585]

54. Shen Y, Boivin R, Yoneda N, Du H, Schiller S, Matsushima T, Goto M, Shirota H, Gusovsky F, Lemelin C et al.. (2010) Discovery of anti-inflammatory clinical candidate E6201, inspired from resorcylic lactone LL-Z1640-2, III. Bioorg Med Chem Lett, 20 (10): 3155-7. [PMID:20399648]

55. Silacci M, Lembke W, Woods R, Attinger-Toller I, Baenziger-Tobler N, Batey S, Santimaria R, von der Bey U, Koenig-Friedrich S, Zha W et al.. (2016) Discovery and characterization of COVA322, a clinical-stage bispecific TNF/IL-17A inhibitor for the treatment of inflammatory diseases. MAbs, 8 (1): 141-9. [PMID:26390837]

56. Smith SH, Jayawickreme C, Rickard DJ, Nicodeme E, Bui T, Simmons C, Coquery CM, Neil J, Pryor WM, Mayhew D et al.. (2017) Tapinarof Is a Natural AhR Agonist that Resolves Skin Inflammation in Mice and Humans. J Invest Dermatol, 137 (10): 2110-2119. [PMID:28595996]

57. Smith SH, Peredo CE, Takeda Y, Bui T, Neil J, Rickard D, Millerman E, Therrien JP, Nicodeme E, Brusq JM et al.. (2016) Development of a Topical Treatment for Psoriasis Targeting RORγ: From Bench to Skin. PLoS ONE, 11 (2): e0147979. [PMID:26870941]

58. Sofen H, Smith S, Matheson RT, Leonardi CL, Calderon C, Brodmerkel C, Li K, Campbell K, Marciniak Jr SJ, Wasfi Y et al.. (2014) Guselkumab (an IL-23-specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis. J Allergy Clin Immunol, 133 (4): 1032-40. [PMID:24679469]

59. Song IH, Rudwaleit M. (2013) Certolizumab pegol in axial spondyloarthritis. Expert Rev Clin Immunol, 9 (12): 1161-72. [PMID:24215406]

60. Sugahara K, Maeda Y, Shimano K, Mogami A, Kataoka H, Ogawa K, Hikida K, Kumagai H, Asayama M, Yamamoto T et al.. (2017) Amiselimod, a novel sphingosine 1-phosphate receptor-1 modulator, has potent therapeutic efficacy for autoimmune diseases, with low bradycardia risk. Br J Pharmacol, 174 (1): 15-27. [PMID:27714763]

61. Taylor PC, Saurigny D, Vencovsky J, Takeuchi T, Nakamura T, Matsievskaia G, Hunt B, Wagner T, Souberbielle B, NEXUS Study Group. (2019) Efficacy and safety of namilumab, a human monoclonal antibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) ligand in patients with rheumatoid arthritis (RA) with either an inadequate response to background methotrexate therapy or an inadequate response or intolerance to an anti-TNF (tumour necrosis factor) biologic therapy: a randomized, controlled trial. Arthritis Res Ther, 21 (1): 101. [PMID:30999929]

62. Thurmond RL, Greenspan A, Radziszewski W, Xu XL, Miao Y, Chen B, Ge T, Zhou B, Baker DG, Pavlova D et al.. (2016) Toreforant, A Histamine H4 Receptor Antagonist, in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy: Results of 2 Phase II Studies. J Rheumatol, 43 (9): 1637-42. [PMID:27422891]

63. Tocker J, Mehlin C, Lim AC. (2010) Neutralizing determinants of IL-17 Receptor A and antibodies that bind thereto. Patent number: US7767206. Assignee: Amgen Inc.. Priority date: 02/10/2006. Publication date: 03/08/2010.

64. Towne JE, Cheng JD, O'neill JC, Zhang Y, Sun Y, Cerne H, Piper DE, Ketcherm RR. (2011) Human il-23 antigen binding proteins. Patent number: WO2011056600. Assignee: Amgen Inc.. Priority date: 26/10/2009. Publication date: 12/05/2011.

65. Varani K, Padovan M, Govoni M, Vincenzi F, Trotta F, Borea PA. (2010) The role of adenosine receptors in rheumatoid arthritis. Autoimmun Rev, 10 (2): 61-4. [PMID:20691813]

66. Watz H, Bock D, Meyer M, Schierhorn K, Vollhardt K, Woischwill C, Pedersen F, Kirsten A, Beeh KM, Meyer-Sabellek W et al.. (2013) Inhaled pan-selectin antagonist Bimosiamose attenuates airway inflammation in COPD. Pulm Pharmacol Ther, 26 (2): 265-70. [PMID:23257347]

67. Zhou H, Jang H, Fleischmann RM, Bouman-Thio E, Xu Z, Marini JC, Pendley C, Jiao Q, Shankar G, Marciniak SJ et al.. (2007) Pharmacokinetics and safety of golimumab, a fully human anti-TNF-alpha monoclonal antibody, in subjects with rheumatoid arthritis. J Clin Pharmacol, 47 (3): 383-96. [PMID:17322150]