FM-381

FM-381 is a potent covalent reversible inhibitor of JAK3 targeting the unique Cys909. FM-381 has an IC50 of 127 pM for JAK3, with 410, 2700 and 3600-fold selectivity over JAK1, JAK2 and TYK2, respectively.

Product information

CAS Number: 2226521-65-7

Molecular Weight: 428.49

Formula: C24H24N6O2

Chemical Name: (2E)-2-cyano-3-(5-{3-cyclohexyl-3, 5, 8, 10-tetraazatricyclo[7.3.0.0, ]dodeca-1, 4, 6, 8, 11-pentaen-4-yl}furan-2-yl)-N, N-dimethylprop-2-enamide

Smiles: CN(C)C(=O)/C(=C/C1=CC=C(O1)C1=NC2=CN=C3NC=CC3=C2N1C1CCCCC1)/C#N

InChiKey: GJMZWYLOARVASY-NTCAYCPXSA-N

InChi: InChI=1S/C24H24N6O2/c1-29(2)24(31)15(13-25)12-17-8-9-20(32-17)23-28-19-14-27-22-18(10-11-26-22)21(19)30(23)16-6-4-3-5-7-16/h8-12,14,16H,3-7H2,1-2H3,(H,26,27)/b15-12+

Technical Data

Appearance: Solid Power

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

Solubility: DMSO : 8.33 mg/mL (19.44 mM; Need ultrasonic)

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:

FM-381 is screened against a panel of 410 kinases at concentrations of 100 nM and 500 nM. FM-381 has no relevant effect on the activity of any tested kinases except JAK3 at a concentration of 100 nM. At 500 nM, FM-381 moderately inhibits 11 other kinases besides JAK3 with residual activities below 50%. FM-381 is found to be inactive in a selectivity panel of frequently hit BRDs (BRD4, BRPF, CECR, FALZ, TAF1, BRD9). FM-381 selectively inhibits JAK3 signaling in human CD4+ T Cells. FM-381 shows an apparent EC50 of 100 nM in a dose dependent BRET assay and blocks IL2 stimulated (JAK3/JAK1 dependent) STAT5 phosphorylation at 100 nM, but not JAK3 independent IL6 (JAK1/2/TYK dependent) stimulated STAT3 signalling in human CD4+ T cells up to 1 µM.

References:

1. Forster M, et al. Selective JAK3 Inhibitors with a Covalent Reversible Binding Mode Targeting a New Induced Fit Binding Pocket. Cell Chem Biol. 2016 Nov 17;23(11):1335-1340.

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