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Ulcerative colitis

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:1054
Name:Ulcerative colitis
Associated with:3 targets
1 immuno-relevant target
24 immuno-relevant ligands
Synonyms
Inflammatory bowel disease 1; IBD1
Database Links
Disease Ontology: DOID:8577
OMIM: 266600
Orphanet: ORPHA771

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
TLR4
nucleotide binding oligomerization domain containing 2
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 UC.

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
mesalazine
Immuno Disease Comments: Approved drug for UC treatment and symptom prophylaxis.
Clinical Use: Mesalazine is used to treat active ulcerative colitis and to prevent symptom recurrence. It may also be used for the management of other types of inflammatory bowel disease (e.g. Crohn's disease). | View clinical data
olamkicept
Immuno Disease Comments: Phase 2 clinical candidate for active UC- see NCT03235752.
Clinical Use: A Phase 2 clinical trial evaluating olamkicept (using research code TJ301) in patients with active ulcerative colitis is registered with ClinicalTrials.gov and is currently in the recruiting stage (as of April 2019- see NCT03235752). | View clinical data
prednisolone
Immuno Disease Comments: Glucocorticoid drug used to treat many inflammatory condtions including UC.
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
ACTH
Immuno Disease Comments: A corticotropin used to treat the symptoms of many inflammatory disorders including UC
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
IL-22 29
Immuno Disease Comments: Enhanced activity of IL-22-regulated molecular pathways has been detected in ulcerative colitis patients whose disease is resistant to treatment with the anti-IL-23 monoclonal antibody ustekinumab.
Clinical Use: An IL-22-Fc fusion protein (Efmarodocokin alfa/UTTR1147A/RG7880; Genentech) has been advanced to clinical evaluation. | View clinical data
infliximab
Immuno Disease Comments: Approved monoclonal antibody therapy for UC.
Clinical Use: Used in the management of rheumatoid arthritis (in combination with ), ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn's disease [43] and ulcerative colitis. A subcutaneous formulation is available for use as maintenance option for patients with Crohn's disease/ulcerative colitis following intravenously infliximab therapy. | 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) [33]. 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
golimumab
Immuno Disease Comments: An anti-TNFα therapy approved for CD.
Clinical Use: Used in adults with various inflammatory conditions [49] e.g. moderate to severe active rheumatoid arthritis [15], active psoriatic arthritis, active ankylosing spondylitis and moderate to severe ulcerative colitis. | View clinical data
corticotropin zinc hydroxide
Immuno Disease Comments: Historically used to treat UC, with use now discontinued.
Clinical Use: Historical clinical uses include the treatment of ulcerative colitis and other colonic disorders [32] and therapy of some collagen diseases [2]. | View clinical data
azathioprine
Immuno Disease Comments: Approved drug for UC.
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. The EMA approved azathioprine to prevent graft rejection in July 2021. | View clinical data
Bioactivity Comments: Azathioprine is reported to inhibit peptidylarginine deiminase 4 (PADI4), albeit with very low in vitro affinity [19]. PADI enzymes catalyze the hydrolytic deimination of protein arginine to produce protein citrulline and ammonia [14] 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 UC.
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 [38]. Soler et al. (2009) also show by FACS analysis that vedolizumab binds specifically to cells exogenously expressing the α4 and β7 intergrin proteins [38]. | View biological activity
peficitinib
Immuno Disease Comments: Phase 2 trial NCT01959282 in UC has been completed.
Clinical Use: Peficitinib was approved as a treatment for rheumatoid arthritis in 2019 [21], but is not yet (March 2021) approved by the FDA or EMA. | View clinical data
Bioactivity Comments: Note that some bioactivity data may be generated using peficitinib hydrobromide (PubChem CID 67998300). We have tagged JAK3 as the primary molecular target for this compound for data metric purposes only, and fully acknowledge its pan-JAK activity. | View biological activity
etrolizumab
Immuno Disease Comments: Phase 3 clinical candidate for UC.
Clinical Use: Etrolizumab was progressed to Phase 3 clinical trials as a potential treatment for Crohn's disease and ulcerative colitis (UC) [44]. All four of the UC trials have completed (as of August 2020), with mixed and somewhat dissapointing results, although nothing has yet been published (see Fierce Biotech summary here). At this time etrolizumab trials in Crohn's are still proceeding. | View clinical data
Bioactivity Comments: hu504.32R inhibits cell adhesion in assays performed as part of the patent application [10]; 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
GLPG0974
Immuno Disease Comments: Phase 2 clinical candidate for UC; no active clinical trials.
Clinical Use: A Phase 2 clinical trial evaluating GLPG0974 in ulcerative colitis has been completed (NCT01829321). Safety, pharmacokinetics and pharmacodynamics of GLPG0974 in healthy subjects are reported in [25]. However, despite mediating an inhibition of neutrophil influx, GLPG0974 failed to reach the study endpoint in ptients with ulcerative colitis. | View clinical data
Bioactivity Comments: GLPG0974 is reported to be selective for FFA2 [30] in a panel of 55 receptors, ion channels, and transporters tested in the Cerep ExpresSProfile selectivity set [4]. | View biological activity
ozanimod
Immuno Disease Comments: Phase 3 clinical candidate for UC (see NCT02531126).
Clinical Use: Ozanimod was progressed to Phase 3 clinical evaluation for its potential immunomodulating effects in relapsing multiple sclerosis (RMS) [6] and ulcerative colitis [1]. In late March 2020 the FDA approved ozanimod (0.92 mg) for the treatment of adults with RMS, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. EMA approval followed on May 20th of the same year. | View clinical data
Bioactivity Comments: Ozanimod is metabolized to , a compound which retains an activity profile indistinguishable from its parent [40]. | View biological activity
eldelumab
Immuno Disease Comments: No progress beyond Phase 2 trial.
Clinical Use: Eldelumab has been evaluated in Phase 2 clinical trials for rheumatoid arthritis [48] and ulcerative colitis (NCT00656890) [22]. The antibody showed efficacy in both conditions. | View clinical data
Bioactivity Comments: Eldelumab does not bind other identified CXCR3 ligands (a.k.a. MIG) and (a.k.a. ITAC) [7]. | 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
deflazacort
Immuno Disease Comments: Approved corticosteroid that can be prescribed for UC.
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 by the FDA as a treatment for Duchenne muscular dystrophy [12]. | View clinical data
Bioactivity Comments: In vitro binding to rat kidney, thymus and liver glucocorticoid receptors is reported in [20]. | View biological activity
GSK2982772
Immuno Disease Comments: Clinical candidate in UC.
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 [13]. | View biological activity
ritlecitinib
Immuno Disease Comments: Phase 2 clinical candidate for UC (NCT02958865).
Clinical Use: PF-06651600 completed Phase 2 clinical trials for rheumatoid arthritis and ulcerative colitis and was advanced to Phase 2b/3 in alopecia areata patients (the ALLEGRO study). Click here to link to ClinicalTrials.gov's full list of PF-06651600 trials. In June 2023 the FDA approved ritlecitinib to treat severe alopecia areata, based on positive efficacy results from the ALLEGRO study [18]. The UK's HMRA approved the drug for this indication in November 2023. | 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) [41].
ATP concentration for JAK3 is 4 μM at Km and for JAK1 is 40 μM at Km, but some assays reported in [41] were carried out at 1 mM ATP . | View biological activity
ontamalimab 45
Immuno Disease Comments: Phase 2 clinical candidate for UC (see NCT01771809).
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. in 2017 [45] | 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 [47]. | View biological activity
tofacitinib
Immuno Disease Comments: Approved by the FDA for the treatment of UC.
Clinical Use: Tofacitinib was intiailly approved for the treatment of rheumatoid arthritis. Marketed formulations contain tofacitinib citrate (PubChem CID 10174505).
In Feb 2016 Xelanj XR® was FDA approved as the first once-daily oral JAK inhibitor for rheumatoid arthritis.
In June 2018, FDA approval was expanded to include treatment of patients with moderate to severe ulcerative colitis (UC), subsequent to results from the Phase 3 OCTAVE studies, in which treatment of UC patients with tofacitinib met all primary endpoints and induced significant disase remission [24,28,34]. Xelanj XR® is not approved for UC.

A report in JCI Insight in September 2016 suggests that tofacitinib-induced immunosuppression can stimulate significant hair regrowth in patients with the autoimmune condition alopecia areata [17], although more extensive studies would need to be conducted before the drug could be approved for this indication. Click here to link to a list of tofacitinib/alopecia trials registered with ClinicalTrials.gov. | View clinical data
Bioactivity Comments: Like many first generation kinase inhibitors tofacitinib exhibits a high degree of broad kinome selectivity but is in reality a pan-JAK-inhibitor. Additional kinases inhibited by tofacitinib in biochemical and cellular assays are described in [26]. Tofacitinib is also reported to exhibit immunosuppressive activity which prevents organ rejection in mice and primates [5].
Despite clinical efficacy in ulcerative colitis, tofacitinib did not show significant efficacy as an induction and maintenance therapy over placebo, in Crohn's disease patients (as evaluated in Phase 2 studies NCT01393626 and NCT01393899) [27]. | View biological activity
ustekinumab 35
Immuno Disease Comments: FDA approved for the treatment of moderate-severe UC in October 2019. Results from Phase 3 clinical trial NCT02407236 showed that ustekinumab was more effective than placebo as measured by induction and maintainance of clinical remission.
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 [11]) 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
upadacitinib
Immuno Disease Comments: Phase 3 clinical candidate for UC- see NCT02819635
Clinical Use: Upadacitinib (ABT-494) completed successful Phase 3 clinical evaluation for rheumatoid arthritis (RA) [9,23,37], and was granted FDA approval in August 2019 and EMA approval in December 2019, as a treatment for patients with moderate-severe active RA that is inadequately controlled by [8]. Evaluation of upadacitinib's potential in additional immune-mediated conditions (psoriatic arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis, atopic dermatitis, SLE and temporal arteritis) are ongoing [31,36,42]. Click here to link to ClinicalTrials.gov's list of ABT-494 studies.
Abbvie reported (in a press release) that upadacitinib met its primary and secondary endpoints in Phase 3 evaluation in psoriatic arthritis (October 2019). No new safety risks were detected. Depending on the dose administered, 25-29% of patients achieved minimal disease activity at week 24 of the study. Formal publication of these results will follow.
FDA approval was expanded in May 2023, to include treatment of moderate-severe active Crohn's disease that has not responded to anti-TNFα drugs. | View clinical data
Bioactivity Comments: In a kinase screening panel, only two other kinases, Rock1 and Rock2 have IC50s below 1000nM [46]. | View biological activity
mirikizumab 16
Immuno Disease Comments: Approved drug for moderate to severe UC
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 [16]. | 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

References

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