| Identification | Back Directory | [Name]
BMS-986142 | [CAS]
1643368-58-4 | [Synonyms]
BMS-986142
BMS-986142;BMS 986142;BMS986142
(2S,5R)-6-fluoro-5-[(3S)-3-(8-fluoro-1,4-dihydro-1-methyl-2,4-dioxo-3(2H)-quinazolinyl)-2-methylphenyl]-2,3,4,9-tetrahydro-2-(1-hydroxy-1-methylethyl)-1H-Carbazole-8-carboxamide
1H-Carbazole-8-carboxamide, 6-fluoro-5-[(3S)-3-(8-fluoro-1,4-dihydro-1-methyl-2,4-dioxo-3(2H)-quinazolinyl)-2-methylphenyl]-2,3,4,9-tetrahydro-2-(1-hydroxy-1-methylethyl)-, (2S,5R)- | [Molecular Formula]
C32H30F2N4O4 | [MOL File]
1643368-58-4.mol | [Molecular Weight]
572.6 |
| Chemical Properties | Back Directory | [Boiling point ]
746.5±70.0 °C(Predicted) | [density ]
1.394±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO:76.67(Max Conc. mg/mL);133.9(Max Conc. mM)
DMSO:PBS (pH 7.2) (1:3):0.25(Max Conc. mg/mL);0.44(Max Conc. mM)
DMF:30.0(Max Conc. mg/mL);52.39(Max Conc. mM)
Ethanol:15.0(Max Conc. mg/mL);26.2(Max Conc. mM) | [form ]
A crystalline solid | [pka]
15.03±0.29(Predicted) | [color ]
White to off-white | [InChIKey]
ZRYMMWAJAFUANM-UHFFFAOYSA-N | [SMILES]
FC1=CC(C(=O)N)=C2NC3CC(C(O)(C)C)CCC=3C2=C1C1C=CC=C(N2C(N(C)C3=C(C=CC=C3C2=O)F)=O)C=1C |
| Hazard Information | Back Directory | [Uses]
BMS-986142 is a potent and highly selective reversible inhibitor of Bruton's tyrosine kinase (BTK) with an IC50 of 0.5 nM. | [in vivo]
BMS-986142 at 4, 10, and 30 mg/kg results in dose-dependent reductions of 26%, 43%, and 79% in clinically evident disease, respectively, at the end of the study. Interestingly, 4 mg/kg BMS-986142 provides an additive benefit in clinical scores (54% inhibition) when co-administered with MTX versus 19% inhibition with MTX alone. Co-administration of BMS-986142 at 4 mg/kg with MTX result in a 53% reduction in inflammation and bone resorption compared with 24% and 10%, respectively, with either drug alone. Furthermore, serum anti-collagen II IgG titers are significantly inhibited with 10 and 30 mg/kg BMS-986142. BMS-986142 also produces dose-dependent reductions in clinical scores when administration is delayed until the collagen booster on day 21. BMS-986142 doses of 2, 4, and 25 mg/kg in this therapeutic dosing regimen result in clinical score reductions of 17%, 37%, and 67%, respectively, at the end of the study[2]. | [storage]
Store at -20°C | [References]
[1] Watterson SH, et al. Discovery of 6-Fluoro-5-(R)-(3-(S)-(8-fluoro-1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-2-methylphenyl)-2-(S)-(2-hydroxypropan-2-yl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide (BMS-986142): A Reversible Inhibitor of Bruton's Tyrosine Kinase (BTK) Conformationally Constrained by Two Locked Atropisomers. J Med Chem. 2016 Oct 13;59(19):9173-9200.
[2] Kathleen M. Gillooly, et al. Bruton'styrosine kinase inhibitor BMS-986142 in experimental models of rheumatoid arthritis enhances efficacy of agents representing clinical standard-of-care. PLoS One. 2017; 12(7): e0181782. DOI:10.1371/journal.pone.0181782 |
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| Company Name: |
BOC Sciences
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| Tel: |
1-631-485-4226; 16314854226 |
| Website: |
https://www.bocsci.com |
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