Uveitis

Disease ID:1198
Name:Uveitis
Associated with:0 target
6 immuno-relevant ligands
Description
Inflammation of the uvea or uveal tract; includes anterior uveitis, intermediate uveitis and posterior uveitis.
Database Links
Disease Ontology: DOID:13141

Targets

No target related data available for Uveitis

Ligands

Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
piclidenoson
Immuno Disease Comments: Clinical candidate for uveitis (Phase 2 NCT01905124)
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 III, NCT02647762 [9]; plaque psoriasis, Phase II [1]; uveitis Phase II) and glaucoma (Phase II, NCT01033422 [3]). | View clinical data
gevokizumab
Immuno Disease Comments: Approved therapeutic for uveitis.
Clinical Use: This monoclonal antibody drug has been granted orphan status in the US (FDA 2012) and EU (EMA 2013) for the treatment of the rare disease, chronic non-infectious uveitis (including that associated with Behçet’s disease). | View clinical data
Bioactivity Comments: The inhibitory effects gevokizumab of arise from a classic allosteric ternary complex mechanism whereby the antibody binds to the orthosteric agonist IL-1β, modulating the interaction with the orthosteric site on the receptor [4,6].
Sequence analysis of the peptide sequence of gevokizumab indicate a match for sequence ID 15 from patent US7531166 [5], suggesting that gevokizumab derives from clone AB7. Data for clone AB7 is included in the interaction table below. | View biological activity
rimexolone
Immuno Disease Comments: Approved drug for uveitis.
Clinical Use: Used to treat inflammation of the eye. | View clinical data
difluprednate
Immuno Disease Comments: Specifically approved for anterior uveitis.
Clinical Use: Approved to treat eye pain and inflammation following opthalmic surgery and to treat anterior uveitis. | View clinical data
Bioactivity Comments: Difluprednate has a reported Ki of 0.78nM [7] in a glucocorticoid receptor binding assay. As it is clear from the structure of this drug that it is a glucocorticoid receptor agonist we have tagged this receptor as the primary drug target, despite being unable to identify publicly available bioactivity data at the human glucocorticoid receptor. | View biological activity
sarilumab
Immuno Disease Comments: Completed Phase 2 clinical trial for non-infectious uveitis (see NCT01900431).
Clinical Use: Sarilumab was granted FDA approval as a treatment for moderate to severe active RA in May 2017 (with EMA approval granted in June 2017), following evaluation in several clinical trials, either as a monotherapy (eg NCT02121210) or in combination with other drugs such as , , and .
Click here to link to ClinicalTrials.gov's listing of Phase III sarilumab trials. A Phase II study for non-infectious uveitis (NCT01900431) has been completed, whereas a Phase II extension study (NCT01118728) for ankylosing spondylitis was terminated. | View clinical data
gevokizumab 2,8
Immuno Disease Comments: Gevokizumab is a FDA and EMA orphan drug for the management of chronic non-infectious uveitis.
Clinical Use: This monoclonal antibody drug has been granted orphan status in the US (FDA 2012) and EU (EMA 2013) for the treatment of the rare disease, chronic non-infectious uveitis (including that associated with Behçet’s disease). | View clinical data
Bioactivity Comments: The inhibitory effects gevokizumab of arise from a classic allosteric ternary complex mechanism whereby the antibody binds to the orthosteric agonist IL-1β, modulating the interaction with the orthosteric site on the receptor [4,6].
Sequence analysis of the peptide sequence of gevokizumab indicate a match for sequence ID 15 from patent US7531166 [5], suggesting that gevokizumab derives from clone AB7. Data for clone AB7 is included in the interaction table below. | View biological activity

References

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1. 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]

2. EMA. Rare disease (orphan) designations- gevokizumab. Accessed on 02/04/2018. Modified on 02/04/2018. European Medicines Agency, http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/landing/orphan_search.jsp&mid=WC0b01ac058001d12b&source=homeMedSearch&keyword=gevokizumab&isNewQuery=true

3. 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]

4. Issafras H, Corbin JA, Goldfine ID, Roell MK. (2014) Detailed mechanistic analysis of gevokizumab, an allosteric anti-IL-1β antibody with differential receptor-modulating properties. J. Pharmacol. Exp. Ther., 348 (1): 202-15. [PMID:24194526]

5. Masat L, Haak-Frendscho M, Chen G, Horwitz A, Roell M. (2009) IL-1β binding antibodies and fragments thereof. Patent number: US7531166. Assignee: Xoma Technology, Ltd. Priority date: 27/02/2015. Publication date: 12/03/2010.

6. Roell MK, Issafras H, Bauer RJ, Michelson KS, Mendoza N, Vanegas SI, Gross LM, Larsen PD, Bedinger DH, Bohmann DJ et al.. (2010) Kinetic approach to pathway attenuation using XOMA 052, a regulatory therapeutic antibody that modulates interleukin-1beta activity. J. Biol. Chem., 285 (27): 20607-14. [PMID:20410301]

7. Tajika T, Waki M, Tsuzuki M, Kida T, Sakaki H. (2011) Pharmacokinetic features of difluprednate ophthalmic emulsion in rabbits as determined by glucocorticoid receptor-binding bioassay. J Ocul Pharmacol Ther, 27 (1): 29-34. [PMID:21182429]

8. US FDA. Gevokizumab orphan drug designations. Accessed on 02/04/2018. Modified on 02/04/2018. FDA Orphan Drug Designations and Approvals, https://www.accessdata.fda.gov/scripts/opdlisting/oopd/listResult.cfm

9. 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]