Crohn's disease

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

Targets

TLR4
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.

Ligands

Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
ozanimod
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
mirikizumab
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
natalizumab
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
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 [27]. | View biological activity
prednisolone
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
adalimumab
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]. | View clinical data
infliximab
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 [26] 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
azathioprine
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
vedolizumab
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
AZD9056
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
deflazacort
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
filgotinib
Immuno Disease Comments: Phase 2 clinical candidate for both perianal fistulizing (NCT03077412) and small bowel (NCT03046056) CD.
Clinical Use: Filgotinib is in Phase II clinical trial for rheumatoid arthritis and Crohn's disease. Click here to link to ClinicalTrials.gov's complete listing of filgotinib Phase II trials. | View clinical data
mongersen
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
etrolizumab
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 [28]. | 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
dectrekumab
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
risankizumab
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
vercirnon
Immuno Disease Comments: Failed to show clinical efficiency in Phase 3 trials.
Clinical Use: Three out of four Phase III 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 [31]. | View biological activity
briakinumab
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 ClinicalTrials.gov) 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
upadacitinib
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 ClinicalTrials.gov'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 [30]. | View biological activity
brazikumab
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 [25]. In binding affinity experiments using recombinant human IL-23, all of the chosen antibodies produced equilibrium dissociation constant (KD) values <4pM [25]. | View biological activity
amiselimod
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
PF-00547659
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) [29] | 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 [32]. | View biological activity
teduglutide
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 [8,33]. | View clinical data

References

Show »

1. 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.

2. 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]

3. Fong S, Dennis MS. (2009) Humanized anti-beta7 antagonists and uses therefor. Patent number: US7528236 B2. Assignee: Genentech, Inc.. Priority date: 03/09/2004. Publication date: 09/05/2009.

4. Gibbons DL, Abeler-Dörner L, Raine T, Hwang IY, Jandke A, Wencker M, Deban L, Rudd CE, Irving PM, Kehrl JH et al.. (2011) Cutting Edge: Regulator of G protein signaling-1 selectively regulates gut T cell trafficking and colitic potential. J. Immunol., 187 (5): 2067-71. [PMID:21795595]

5. Griggs RC, Miller JP, Greenberg CR, Fehlings DL, Pestronk A, Mendell JR, Moxley 3rd RT, King W, Kissel JT, Cwik V et al.. (2016) Efficacy and safety of deflazacort vs prednisone and placebo for Duchenne muscular dystrophy. Neurology, 87 (20): 2123-2131. [PMID:27566742]

6. Hommes DW, Mikhajlova TL, Stoinov S, Stimac D, Vucelic B, Lonovics J, Zákuciová M, D'Haens G, Van Assche G, Ba S et al.. (2006) Fontolizumab, a humanised anti-interferon gamma antibody, demonstrates safety and clinical activity in patients with moderate to severe Crohn's disease. Gut, 55 (8): 1131-7. [PMID:16507585]

7. 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]

8. Jeppesen PB. (2012) Teduglutide, a novel glucagon-like peptide 2 analog, in the treatment of patients with short bowel syndrome. Therap Adv Gastroenterol, 5 (3): 159-71. [PMID:22570676]

9. Jones JE, Causey CP, Knuckley B, Slack-Noyes JL, Thompson PR. (2009) Protein arginine deiminase 4 (PAD4): Current understanding and future therapeutic potential. Curr Opin Drug Discov Devel, 12 (5): 616-27. [PMID:19736621]

10. Kimball AB, Gordon KB, Langley RG, Menter A, Chartash EK, Valdes J, ABT-874 Psoriasis Study Investigators. (2008) Safety and efficacy of ABT-874, a fully human interleukin 12/23 monoclonal antibody, in the treatment of moderate to severe chronic plaque psoriasis: results of a randomized, placebo-controlled, phase 2 trial. Arch Dermatol, 144 (2): 200-7. [PMID:18283176]

11. 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.

12. Knuckley B, Luo Y, Thompson PR. (2008) Profiling Protein Arginine Deiminase 4 (PAD4): a novel screen to identify PAD4 inhibitors. Bioorg. Med. Chem., 16 (2): 739-45. [PMID:17964793]

13. 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]

14. Luzzani F, Glässer A. (1981) Differential binding in vitro to glucocorticoid receptors of deflazacort and prednisolone. Eur. J. Pharmacol., 76 (4): 427-30. [PMID:7327211]

15. Monteleone G, Neurath MF, Ardizzone S, Di Sabatino A, Fantini MC, Castiglione F, Scribano ML, Armuzzi A, Caprioli F, Sturniolo GC et al.. (2015) Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease. N. Engl. J. Med., 372 (12): 1104-13. [PMID:25785968]

16. 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]

17. Reinisch W, de Villiers W, Bene L, Simon L, Rácz I, Katz S, Altorjay I, Feagan B, Riff D, Bernstein CN et al.. (2010) Fontolizumab in moderate to severe Crohn's disease: a phase 2, randomized, double-blind, placebo-controlled, multiple-dose study. Inflamm. Bowel Dis., 16 (2): 233-42. [PMID:19637334]

18. Rothenberg ME, Wen T, Greenberg A, Alpan O, Enav B, Hirano I, Nadeau K, Kaiser S, Peters T, Perez A et al.. (2015) Intravenous anti-IL-13 mAb QAX576 for the treatment of eosinophilic esophagitis. J. Allergy Clin. Immunol., 135 (2): 500-7. [PMID:25226850]

19. Rutgeerts P, D'Haens G, Targan S, Vasiliauskas E, Hanauer SB, Present DH, Mayer L, Van Hogezand RA, Braakman T, DeWoody KL et al.. (1999) Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn's disease. Gastroenterology, 117 (4): 761-9. [PMID:10500056]

20. Soler D, Chapman T, Yang LL, Wyant T, Egan R, Fedyk ER. (2009) The binding specificity and selective antagonism of vedolizumab, an anti-alpha4beta7 integrin therapeutic antibody in development for inflammatory bowel diseases. J. Pharmacol. Exp. Ther., 330 (3): 864-75. [PMID:19509315]

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

22. 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]

23. Takahashi S, Andreoletti G, Chen R, Munehira Y, Batra A, Afzal NA, Beattie RM, Bernstein JA, Ennis S, Snyder M. (2017) De novo and rare mutations in the HSPA1L heat shock gene associated with inflammatory bowel disease. Genome Med, 9 (1): 8. [PMID:28126021]

24. Taylor Meadows KR, Steinberg MW, Clemons B, Stokes ME, Opiteck GJ, Peach R, Scott FL. (2018) Ozanimod (RPC1063), a selective S1PR1 and S1PR5 modulator, reduces chronic inflammation and alleviates kidney pathology in murine systemic lupus erythematosus. PLoS ONE, 13 (4): e0193236. [PMID:29608575]

25. 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.

26. van Dullemen HM, van Deventer SJ, Hommes DW, Bijl HA, Jansen J, Tytgat GN, Woody J. (1995) Treatment of Crohn's disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology, 109 (1): 129-35. [PMID:7797011]

27. Vasquez M, Landolfi NF, Tsurushita N, Queen CL. (2001) Humanized antibodies to γ-interferon. Patent number: US6329511B1. Assignee: Protein Design Labs Inc. Priority date: 01/12/1998. Publication date: 11/12/2001.

28. Vermeire S, O'Byrne S, Keir M, Williams M, Lu TT, Mansfield JC, Lamb CA, Feagan BG, Panes J, Salas A et al.. (2014) Etrolizumab as induction therapy for ulcerative colitis: a randomised, controlled, phase 2 trial. Lancet, 384 (9940): 309-18. [PMID:24814090]

29. Vermeire S, Sandborn WJ, Danese S, Hébuterne X, Salzberg BA, Klopocka M, Tarabar D, Vanasek T, Greguš M, Hellstern PA et al.. (2017) Anti-MAdCAM antibody (PF-00547659) for ulcerative colitis (TURANDOT): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet, 390 (10090): 135-144. [PMID:28527704]

30. Voss JW, Camp HS, Padley RJ. (2015) Jak1 selective inhibitor and uses thereof. Patent number: WO2015061665. Assignee: Abbvie Inc.. Priority date: 24/10/2013. Publication date: 30/04/2015.

31. Walters MJ, Wang Y, Lai N, Baumgart T, Zhao BN, Dairaghi DJ, Bekker P, Ertl LS, Penfold ME, Jaen JC et al.. (2010) Characterization of CCX282-B, an orally bioavailable antagonist of the CCR9 chemokine receptor, for treatment of inflammatory bowel disease. J. Pharmacol. Exp. Ther., 335 (1): 61-9. [PMID:20660125]

32. Wang M, Kussrow AK, Ocana MF, Chabot JR, Lepsy CS, Bornhop DJ, O'Hara DM. (2017) Physiologically relevant binding affinity quantification of monoclonal antibody PF-00547659 to mucosal addressin cell adhesion molecule for in vitro in vivo correlation. Br. J. Pharmacol., 174 (1): 70-81. [PMID:27760281]

33. Yazbeck R. (2010) Teduglutide, a glucagon-like peptide-2 analog for the treatment of gastrointestinal diseases, including short bowel syndrome. Curr. Opin. Mol. Ther., 12 (6): 798-809. [PMID:21154171]