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
1. Abbvie press release. 
Upadacitinib Meets All Primary and Ranked Secondary Endpoints Including Superiority Versus Adalimumab in Phase 3 Study in Rheumatoid Arthritis.
Accessed on 12/04/2018. Modified on 12/04/2018. https://news.abbvie.com, https://news.abbvie.com/news/upadacitinib-meets-all-primary-and-ranked-secondary-endpoints-including-superiority-versus-adalimumab-in-phase-3-study-in-rheumatoid-arthritis.htm
2. Duggan S, Keam SJ. (2019)
Upadacitinib: First Approval.
Drugs, 79 (16): 1819-1828. [PMID:31642025]
3. Fleischmann R, Pangan AL, Song IH, Mysler E, Bessette L, Peterfy C, Durez P, Ostor AJ, Li Y, Zhou Y et al.. (2019)
Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double-Blind, Randomized Controlled Trial.
Arthritis Rheumatol, 71 (11): 1788-1800. [PMID:31287230]
4. Mohamed MF, Klünder B, Camp HS, Othman AA. (2019)
Exposure-Response Analyses of Upadacitinib Efficacy in Phase II Trials in Rheumatoid Arthritis and Basis for Phase III Dose Selection.
Clin Pharmacol Ther, 106 (6): 1319-1327. [PMID:31194885]
5. Parmentier JM, Voss J, Graff C, Schwartz A, Argiriadi M, Friedman M, Camp HS, Padley RJ, George JS, Hyland D et al.. (2018)
In vitro and in vivo characterization of the JAK1 selectivity of upadacitinib (ABT-494).
BMC Rheumatol, 2: 23. [PMID:30886973]
6. Pérez-Jeldres T, Tyler CJ, Boyer JD, Karuppuchamy T, Yarur A, Giles DA, Yeasmin S, Lundborg L, Sandborn WJ, Patel DR et al.. (2019)
Targeting Cytokine Signaling and Lymphocyte Traffic via Small Molecules in Inflammatory Bowel Disease: JAK Inhibitors and S1PR Agonists.
Front Pharmacol, 10: 212. [PMID:30930775]
7. Shukla T, Sands BE. (2019)
Novel Non-biologic Targets for Inflammatory Bowel Disease.
Curr Gastroenterol Rep, 21 (5): 22. [PMID:31016396]
8. Smolen JS, Pangan AL, Emery P, Rigby W, Tanaka Y, Vargas JI, Zhang Y, Damjanov N, Friedman A, Othman AA et al.. (2019)
Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): a randomised, placebo-controlled, double-blind phase 3 study.
Lancet, 393 (10188): 2303-2311. [PMID:31130260]
9. Torgutalp M, Poddubnyy D. (2018)
Emerging treatment options for spondyloarthritis.
Best Pract Res Clin Rheumatol, 32 (3): 472-484. [PMID:31171316]
10. 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.
11.  AbbVie's Upadacitinib (ABT-494) Meets All Primary and Ranked Secondary Endpoints in Second Phase 3 Study in Rheumatoid Arthritis.
Accessed on 18/09/2017. Modified on 18/09/2017. drugs.com, https://www.drugs.com/clinical_trials/abbvie-s-upadacitinib-abt-494-meets-all-primary-ranked-secondary-endpoints-second-phase-3-study-17607.html