BMS-986195

Product NameBMS-986195
CAS1912445-55-6
MFC20H23FN4O2
MW370.42
EINECS
MOL File1912445-55-6.mol

Chemical Properties

Density	1.32±0.1 g/cm3(Predicted)
storage temp.	Store at -20°C
solubility	DMSO:87.0(Max Conc. mg/mL);234.86(Max Conc. mM) Ethanol:38.0(Max Conc. mg/mL);102.58(Max Conc. mM)
form	A crystalline solid
pka	11.91±0.20(Predicted)
color	White to off-white
InChI	InChI=1S/C20H23FN4O2/c1-4-6-16(26)24-13-7-5-8-25(10-13)19-15(21)9-14(20(22)27)18-17(19)11(2)12(3)23-18/h9,13,23H,5,7-8,10H2,1-3H3,(H2,22,27)(H,24,26)/t13-/m0/s1
InChIKey	VJPPLCNBDLZIFG-ZDUSSCGKSA-N
SMILES	N1C2=C(C(N3CCC[C@H](NC(=O)C#CC)C3)=C(F)C=C2C(N)=O)C(C)=C1C

Usage And Synthesis

Uses

Branebrutinib (BMS-986195) is a potent inhibitor of BTK with IC50 values of 0.1 nM, 0.9 nM, 1.5 nM, 5 nM for BTK, TEC, BMX, TXK, respectively.

Uses

Branebrutinib (BMS-986195) is a highly potent, selective covalent, irreversible inhibitor of Bruton’s tyrosine kinase (BTK), with an IC50 of 0.1 nM[1][2]. Branebrutinib is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

in vivo

In mice, BMS-986195 demonstrates robust efficacy in murine models of RA including CIA and CAIA, protecting against clinically evident disease, histologic joint damage and bone mineral density loss. In both mice and monkeys, maximal efficacy is observed at doses ≤0.5 mg/kg PO QD, which achieves ≥95% inactivation of BTK in vivo. At similar doses, BMS-986195 is also highly protective against nephritis in the NZB/W mouse model of lupus. To investigate the dynamics of BTK inactivation and resynthesis of BTK, cynomolgus monkeys are given single or multiple doses of BMS-986195. 100% peak inactivation of BTK is obtained with a single administration of BMS-986195 at 0.5 mg/kg PO^[1].

References

[1] JR Burke, et al. BMS-986195 Is a Highly Selective and Rapidly Acting Covalent Inhibitor of Bruton’s Tyrosine Kinase with Robust Efficacy at Low Doses in Preclinical Models of RA and Lupus Nephritis. 2017 ACR/ARHP Annual Meeting, September 18, 2017.
[2] Watterson SH, et al. Discovery of Branebrutinib (BMS-986195): A Strategy for Identifying a Highly Potent and Selective Covalent Inhibitor Providing Rapid in Vivo Inactivation of Bruton's Tyrosine Kinase (BTK). J Med Chem. 2019 Apr 11;62(7):3228-3250. DOI:10.1021/acs.jmedchem.9b00167

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