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
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Summary of Clinical Use Click here for help
Upadacitinib (ABT-494) completed successful Phase 3 clinical evaluation for rheumatoid arthritis (RA) [3-4,8], 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 methotrexate [2]. 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 [6-7,9]. 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.
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