upadacitinib   Click here for help

GtoPdb Ligand ID: 9246

Synonyms: ABT-494 | Rinvoq®
Approved drug Immunopharmacology Ligand
upadacitinib is an approved drug (EMA & FDA (2019))
Compound class: Synthetic organic
Comment: Upadacitinib (ABT-494) is a novel second generation orally active Janus kinase inhibitor with high JAK1 selectivity [5,10]. The chemical structure is claimed as compound 1 in Abbvie's patent WO2015061665 [10]. It was developed for potential clinical efficacy in multiple autoimmune diseases. Its first approval was for the treatment of rheumatoid arthritis [2].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 78.32
Molecular weight 380.16
XLogP 3.06
No. Lipinski's rules broken 0
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Canonical SMILES CCC1CN(CC1c1cnc2n1c1cc[nH]c1nc2)C(=O)NCC(F)(F)F
Isomeric SMILES CC[C@@H]1CN(C[C@@H]1c1cnc2n1c1cc[nH]c1nc2)C(=O)NCC(F)(F)F
InChI InChI=1S/C17H19F3N6O/c1-2-10-7-25(16(27)24-9-17(18,19)20)8-11(10)13-5-22-14-6-23-15-12(26(13)14)3-4-21-15/h3-6,10-11,21H,2,7-9H2,1H3,(H,24,27)/t10-,11+/m1/s1
Immunopharmacology Comments
Upadacitinib (ABT-494) is reported to have met all of its primary and secondary endpoints in Phase 3 clinical trial in patients with DMARD refactory moderate to severe rheumatoid arthritis (RA), or with DMARD intolerance- see this drugs.com webpage report for further details [11]. Abbvie published an online update in April 2018, reporting that a significantly higher proportion of patients given upadacitinib achieved clinical remission compared to placebo controls, and that upadacitinib was more effective in achieving a low disease activity score compared to adalimumab [1].
Immunopharmacology Disease
Disease X-Refs Comment References
Crohn's disease Disease Ontology: DOID:8778
OMIM: 266600
Orphanet: ORPHA206
Phase 3 clinical candidate for CD.
Rheumatoid arthritis Disease Ontology: DOID:7148
OMIM: 180300
FDA approved drug for RA (August 2019).
Temporal arteritis Disease Ontology: DOID:13375
OMIM: 187360
Orphanet: ORPHA397
Phase 3 clinical candidate for temporal arteritis (giant cell arteritis)- see NCT03725202
Psoriatic arthritis Disease Ontology: DOID:9008
Phase 3 clinical candidate for PsA- see NCT03104374
Ulcerative colitis Disease Ontology: DOID:8577
OMIM: 266600
Orphanet: ORPHA771
Phase 3 clinical candidate for UC- see NCT02819635
Atopic dermatitis Disease Ontology: DOID:3310
OMIM: 603165
Phase 3 clinical candidate for AD- see NCT03568318