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Crohn's disease

Disease ID:1016
Name:Crohn's disease
Associated with:4 targets
1 immuno-relevant target
27 immuno-relevant ligands
Crohn disease | Inflammatory bowel disease 1; IBD1
Database Links
Disease Ontology: DOID:8778
OMIM: 266600
Orphanet: ORPHA206


nucleotide binding oligomerization domain containing 2
regulator of G-protein signaling 1
Comments:  Crohn's disease AND ulcerative colitis
References:  4
heat shock protein family A (Hsp70) member 1 like
Comments:  Genetic mutations that cause amino acid changes in the HSPA1L protein have been identified in patients with CD.


Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
Immuno Disease Comments: Phase 2 clinical candidate for CD (see NCT02531113).
Clinical Use: Ozanimod has reached Phase III clinical trial for its potential antiinflammatory effects in relapsing multiple sclerosis and ulcerative colitis. | View clinical data
Bioactivity Comments: Ozanimod is metabolized to , a compound which retains an activity profile indistinguishable from its parent [24]. | View biological activity
Immuno Disease Comments: Approved drug for CD.
Clinical Use: Used in the treatment of relapsing forms of multiple sclerosis, and in the management of Crohn's disease. However, natalizumab is not widely prescribed due to safety concerns around progressive multifocal leukoencephalopathy (PML). | View clinical data
Bioactivity Comments: We have been unable to find affinity data for this antibody from an open access article. | View biological activity
Immuno Disease Comments: Phase 2 clinical candidate for active CD- see NCT02891226.
Clinical Use: Phase 2 clinical trials which will evaluate mirikizumab (as research code LY3074828) in Crohn's disease (NCT02891226), ulcerative colitis (NCT02589665) and plaque psoriasis (NCT02899988) patients are underway. | 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 [1]. 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 [1]. | View biological activity
fontolizumab 6,17
Immuno Disease Comments: Fontolizumab has completed Phase 2 clinical trial in patients with moderate to severe Crohn's disease- see NCT00072943
Clinical Use: Fontolizumab (HuZAF) has completed Phase 2 clinical trial in patients with moderate to severe Crohn's disease (NCT00072943). Results showed that fontolizumab was well tolerated by these patients, and effected increased rates of clinical response and remission compared with placebo [6,17]. A Phase 2 trial in rheumatoid arthritis (NCT00281294) was terminated early because the first phase failed to meet the endpoint. | View clinical data
Bioactivity Comments: Fontolizumab neutralises the proinflammatory activity of IFNγ, as measured by antibody-mediated reduction in IFNγ-induced upregulation of MHC II expression by Hs294T melanoma cells [28]. | View biological activity
Immuno Disease Comments: Glucocorticoid drug used to treat many inflammatory condtions including CD.
Clinical Use: This drug used as an antiinflammatory or immunosuppressive agent and is indicated for the treatment of various inflammatory pathologies, including acute asthma, suppression of inflammatory and allergic disorders, ulcerative colitis, Crohn's disease, idiopathic thrombocytopenic purpura, rheumatoid arthritis, polymyalgia rheumatica, systemic lupus erythematosus and chronic obstructive pulmonary disease (COPD). | View clinical data
Immuno Disease Comments: Anti-TNFα monoclonal antibody therapy approved for Crohn's disease.
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 [7]. The EMA marketing authorisation for adalimumab Trudexa® was withdrawn at the request of the marketing authorisation holder. | View clinical data
Immuno Disease Comments: Approved monoclonal antibody therapy for Crohn's disease.
Clinical Use: Used in the management of rheumatoid arthritis (in combination with ), ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn's disease [27] and ulcerative colitis. | View clinical data
Bioactivity Comments: Infliximab has been reported to induce an anti-chimeric antibody response in almost 15% of Crohn's disease patients (47 tested) [19]. This indicates that as predicited, humans can mount an immune response to whole murine variable domains, and is the underlying rationale promoting the development of clinical antibodies with variable domains with more human character (i.e. humanised or fully human monoclonal developments). | View biological activity
certolizumab pegol
Immuno Disease Comments: An anti-TNFα therapy approved for CD.
Clinical Use: Used to treat rheumatoid arthritis (RA) and Crohn's disease [2]. May also have some effect in related conditions such as axial spondyloarthritis [21]. 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 [16], neutralises the effects mediated by membrane bound TNFα, and inhibits production of IL-1β in monocytes stimulated with LPS. | View biological activity
Immuno Disease Comments: Approved drug for CD.
Clinical Use: Used to reduce organ rejection in transplant patients and to treat autoimmune diseases such as rheumatoid arthritis, Crohn's disease, lupus erythematosus and ulcerative colitis. | View clinical data
Bioactivity Comments: Azathioprine is reported to inhibit peptidylarginine deiminase 4 (PADI4), albeit with very low in vitro affinity [12]. PADI enzymes catalyze the hydrolytic deimination of protein arginine to produce protein citrulline and ammonia [9] and cause chromatin decondensation. Dysregulated PADI4 activity may be involved in cancer progression as it is overexpressed in many malignant tumours, where enhanced chromatin decondensation is involved in promoting pluripotency and stem cell maintenance. | View biological activity
Immuno Disease Comments: Approved therapeutic for CD.
Clinical Use: Approved to treat adult patients with moderate to severe ulcerative colitis or moderate to severe Crohn‘s disease. | View clinical data
Bioactivity Comments: In vitro, vedolizumab inhibits specific binding of α4β7 +ve lymphoma cells to immobilised MADCAM1 or fibronectin with IC50 values of 0.39nM and 0.14nM respectively [20]. Soler et al. (2009) also show by FACS analysis that vedolizumab binds specifically to cells exogenously expressing the α4 and β7 intergrin proteins [20]. | View biological activity
AZ11657312 (salt free)
Immuno Disease Comments: Experimental compound.
Bioactivity Comments: Note that bioactivity will be associated with the hydrochloride salt. Pending publication, the data presented here is derived from the compound's record in AstaZeneca's Open Innovation Pharmacology Toolbox | View biological activity
Immuno Disease Comments: Developed with potential for treating CD, but development was discontinued.
Clinical Use: AZD9056 was developed for the treatment of inflammatory conditions such as rheumatoid arthritis (RA), chronic obstructive pulmonary disease (COPD) and Crohn’s disease. Phase II trial NCT00520572 for RA has been completed. There are no active trials in progress (Nov 2014). | View clinical data
Bioactivity Comments: The NIH National Center for Advancing Translational Sciences (NCATS) record for AZD9056 provides bioactivity data as follows: The IC50 for AZD9056-induced inhibition of pro-inflammatory IL-1β and IL-18 release from human peripheral monocytes is 10-13nM. | View biological activity
Immuno Disease Comments: Phase 2 clinical candidate for both perianal fistulizing (NCT03077412) and small bowel (NCT03046056) CD.
Clinical Use: Filgotinib has advanced to Phase 3 evaluation in patients with rheumatoid arthritis, Crohn's disease and ulcerative colitis. Click here to link to's complete listing of filgotinib studies. | View clinical data
Immuno Disease Comments: Phase 3 clinical candidate for CD (see NCT02641392).
Clinical Use: A Phase II clinical trial has shown promising results in Crohn's disease, with higher rates of remission being reported in patients receiving mongersen compared to those in the placebo group [15]. | View clinical data
Immuno Disease Comments: Phase 3 clinical candidate for CD.
Clinical Use: Etrolizumab is being evaluated in Phase III clinical trial as a potential treatment for Crohn's disease and ulcerative colitis [29]. | View clinical data
Bioactivity Comments: hu504.32R inhibits cell adhesion in assays performed as part of the patent application [3]; inhibiting α4β7-MAdCAM-1-mediated adhesion with an IC50 of 0.075nM, and αEβ7-E-cadherin-mediated adhesion with an IC50 of 3.96nM. | View biological activity
Immuno Disease Comments: Phase 2 trial NCT01316601 in CD has been completed.
Clinical Use: Dectrekumab (QBX258) reached Phase II clinical trial as a potential biologic therapy for several immune conditions, including idiopathic pulmonary fibrosis (IPF), asthma, eosinophilic esophagitis [18] (proof of principle study NCT01022970), Crohn's disease, keloids and allergic rhinitis. As of May 2017, there are no active dectrekumab studies. | View clinical data
Immuno Disease Comments: Phase 3 clinical candidate for CD (see NCT03105102).
Clinical Use: Risankizumab has reached Phase II clinical trial for Crohn's disease (CD), psoriasis, and ankylosing spondylitis (AS). Results from the first-in-human proof-of-concept trial in patients with psoriasis are reported in [13]. | View clinical data
Immuno Disease Comments: Failed to show clinical efficiency in Phase 3 trials.
Clinical Use: Three out of four Phase 3 clinical trials evaluating vercirnon (using research code GSK1605786A) in Crohn's disease were terminated due to lack of efficacy. | View clinical data
Bioactivity Comments: Vercirnon (CCX282-B) inhibits CCL25-directed chemotaxis of CCR9 expressing cells and markers of disease are normalised in a mouse Crohn's disease model treated with vercirnon [32]. | View biological activity
Immuno Disease Comments: Clinical development for CD has been terminated.
Clinical Use: Results from a Phase 2 clinical trial (NCT00292396) evaluating briakinumab in patients with moderate to severe chronic plaque psoriasis are reported in [10]. Several Phase 3 trials comparing briakinumab against placebo, and (two approved anti-psoriatic drugs) for moderate to severe chronic plaque psoriasis (link here to a list of these trials on have been completed. Clinical development of briakinumab for rheumatoid arthritis, Crohn's disease and multiple sclerosis has been terminated. As of May 2017, there are no active clinical trials evaluating this antibody. | View clinical data
Immuno Disease Comments: Phase 3 clinical candidate for CD.
Clinical Use: ABT-494 has reached Phase 3 clinical trial for rheumatoid arthritis (RA). Evaluation of upadacitinib's potential in additional immune-mediated conditions (psoriatic arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis and atopic dermatitis) are ongoing. Click here to link to's list of Phase 3 ABT-494 trilas. | View clinical data
Bioactivity Comments: In a kinase screening panel, only two other kinases, Rock1 and Rock2 have IC50s below 1000nM [31]. | View biological activity
Immuno Disease Comments: Phase 2 clinical candidate for CD (see NCT02574637).
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 [26]. In binding affinity experiments using recombinant human IL-23, all of the chosen antibodies produced equilibrium dissociation constant (KD) values <4pM [26]. | View biological activity
Immuno Disease Comments: Phase 2 clinical candidate for CD.
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 [11]. Affinity for S1P receptors is not provided in the patent. Note that bioactivity is attributed to the active metabolite [22], the prodrug is almost completely inactive at S1P1R. | View biological activity
mucosal addressin cell adhesion molecule 1
Immuno Disease Comments: A gut-specific ligand being investigated as a drug target for inflammatory bowel conditions.
Bioactivity Comments: MAdCAM-1 expression is elevated in intestinal biopsies from experimental models of colitis and from patients with Crohn's disease and ulcerative colitis. | View biological activity
Immuno Disease Comments: Phase 2 clinical candidate for CD (see completed study NCT01298492).
Clinical Use: PF-00547659 has completed Phase 2 clinical trials for ulcerative colitis and Crohn's disease. Results from Phase 2 ulcerative colitis trial NCT01620255 were published by Vermeire et al. (2017) [30] | View clinical data
Bioactivity Comments: PF-00547659 binding exhbits >30-fold difference in target affinity between in vitro SPR (surface plasmon resonance) derived KD and clinically derived KD, thought to be due to conformational restrictions in membrane-bound MAdCAM-1 compared to soluble MAdCAM-1 [33]. | View biological activity
Immuno Disease Comments: Approved corticosteroid that can be prescribed for CD.
Clinical Use: Deflazacort can be prescribed for many inflammatory conditions including asthma, rheumatoid arthritis, Crohn's disease, juvenile chronic arthritis, idiopathic thrombocytopenic purpura, polymyalgia rheumatica, systemic lupus erythematosus and ulcerative colitis. More recently approved to treat Duchenne muscular dystrophy [5]. | View clinical data
Bioactivity Comments: In vitro binding to rat kidney, thymus and liver glucocorticoid receptors is reported in [14]. | View biological activity
Immuno Disease Comments: Teduglutide has completed Phase 2 clinical trials in Crohn's disease patients- see NCT00072839 and the follow on trial NCT00308438
Clinical Use: Teduglutide is used in the treatment of short bowel syndrome [8,34]. | View clinical data
Immuno Disease Comments: Phase 2 clinical candidate for patients with moderate to severe CD (NCT03395184).
Clinical Use: PF-06651600 has completed Phase 2 clinical trials for rheumatoid arthritis and ulcerative colitis and it has advanced to Phase 2b/3 in alopecia areata patients. Click here to link to's full list of PF-06651600 trials. | View clinical data
Bioactivity Comments: PF-06651600 exhibits favourable selectivity against a screening panel of 305 kinases in vitro, and shows measurable inhibition of 7 of the 10 other kinases which share a cysteine residue analogous to Cys-909 in the JAK3 ATP binding site (these were BMX, ITK, TXK, TEC, BTK, BLK and HER4) [25].
ATP concentration for JAK3 is 4 μM at Km and for JAK1 is 40 μM at Km, but some assays reported in [25] were carried out at 1 mM ATP . | View biological activity


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