upadacitinib   

GtoPdb Ligand ID: 9246

Synonyms: ABT-494 | Rinvoq®
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].
2D Structure
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Physico-chemical Properties
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
SMILES / InChI / InChIKey
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
InChI Key WYQFJHHDOKWSHR-MNOVXSKESA-N
Bioactivity Comments
In a kinase screening panel, only two other kinases, Rock1 and Rock2 have IC50s below 1000nM [10].
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
Janus kinase 1 Hs Inhibitor Inhibition 7.4 – 8.5 pIC50 - 10
pIC50 8.5 (IC50 3x10-9 M) [10]
Description: at 1uM ATP in a biochemical assay
pIC50 7.4 (IC50 4.3x10-8 M) [10]
Janus kinase 2 Hs Inhibitor Inhibition 6.9 pIC50 - 10
pIC50 6.9 (IC50 1.2x10-7 M) [10]
Janus kinase 3 Hs Inhibitor Inhibition 5.6 pIC50 - 10
pIC50 5.6 (IC50 2.3x10-6 M) [10]
tyrosine kinase 2 Hs Inhibitor Inhibition 5.3 pIC50 - 10
pIC50 5.3 (IC50 4.7x10-6 M) [10]