Upadacitinib

Upadacitinib (ABT-494) is a potent, orally active and selective Janus kinase 1 (JAK1) inhibitor (IC50=43 nM). Upadacitinib (ABT-494) displays approximately 74 fold selective for JAK1 over JAK2 (200 nM) in cellular assays dependent on specific, relevant cytokines. Upadacitinib (ABT-494) is used in development for the treatment of several autoimmune disorders.

Product information

CAS Number: 1310726-60-3

Molecular Weight: 380.37

Formula: C17H19F3N6O

Synonym:

ABT-494

Chemical Name: (3S, 4R)-3-ethyl-4-{1, 5, 7, 10-tetraazatricyclo[7.3.0.0, ]dodeca-2(6), 3, 7, 9, 11-pentaen-12-yl}-N-(2, 2, 2-trifluoroethyl)pyrrolidine-1-carboxamide

Smiles: CC[C@@H]1CN(C[C@@H]1C1=CN=C2C=NC3NC=CC=3N21)C(=O)NCC(F)(F)F

InChiKey: WYQFJHHDOKWSHR-MNOVXSKESA-N

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

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : ≥ 22 mg/mL (57.84 mM)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

In biochemical assays, Upadacitinib is 74-fold more selective for JAK-1 than for JAK-2 (which is involved in erythropoiesis) and 58-fold more selective for JAK-1 than for JAK-3 (which is involved in immunosurveillance). The enhanced selectivity of Upadacitinib for JAK-1 over JAK-2 and JAK-3 may offer an improved benefit–risk profile in patients with RA range.

In Vivo:

Upadacitinib (0.1-10 mg/kg; oral gavage; twice a day for 10 days) demonstrates efficacy in rat arthritis models.

References:

1. Nakayamada S, et al. Recent Progress in JAK Inhibitors for the Treatment of Rheumatoid Arthritis. BioDrugs. 2016 Oct;30(5):407-419.
2. J. Voss, et al. THU0127 Pharmacodynamics of A Novel JAK1 Selective Inhibitor in Rat Arthritis and Anemia Models and in Healthy Human Subjects. doi 10.1136/annrheumdis-2014-eular.3823.
3. Parmentier JM, et al. In vitro and in vivo characterization of the JAK1 selectivity of upadacitinib (ABT-494). BMC Rheumatol. 2018 Aug 28;2:23.

Products are for research use only. Not for human use.