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BMS-986142

Catalog No.GC31713

A BTK inhibitor

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BMS-986142 Chemical Structure

Cas No.: 1643368-58-4

Size Price Stock Qty
10mM (in 1mL DMSO)
$555.00
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5mg
$441.00
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10mg
$682.00
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25mg
$1,350.00
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50mg
$2,205.00
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100mg
$3,167.00
In stock

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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Animal experiment:

Mice[2]Male DBA/1 mice are injected subcutaneously at the base of the tail with bovine type II collagen (200 μg) admixed. The mice are boosted 21 days later in the same manner. For preventative administration, PO QD dosing is immediately started with BMS-986142 in EtOH: TPGS: PEG300 (5:5:90); for therapeutic administration, start of dosing is delayed until the booster immunization on day 21. For BMS-986142 plus MTX preventative studies, mice receive vehicle; BMS-986142 at 4, 10, or 30 mg/kg; BMS-986142 at 4 mg/kg plus MTX 0.25 mg/kg; or MTX at 0.25 mg/kg daily. For BMS-986142 plus etanercept therapeutic studies, mice receive vehicle daily; BMS-986142 at 2, 4, or 25 mg/kg daily ; BMS-986142 at 2 or 4 mg/kg daily plus etanercept at 15 mg/kg IP twice weekly (BIW); or etanercept at 15 mg/kg IP BIW. For BMS-986142 plus murine cytotoxic T lymphocyte-associated protein 4 immunoglobulin (CTLA-4-Ig) preventative studies, mice receive vehicle daily; BMS-986142 at 10 or 30 mg/kg daily; murine CTLA-4-Ig at 0.05 or 0.2 mg/kg IP BIW; or BMS-986142 at 10 mg/kg daily plus murine CTLA-4-Ig at 0.05 or 0.2 mg/kg IP BIW. Dosing proceed from day 0 through study completion (36 days)[2].

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.

Background

BMS-986142 is a potent and highly selective reversible inhibitor of Bruton's tyrosine kinase (BTK) with an IC50 of 0.5 nM.

BMS-986142 potently inhibits human recombinant BTK with an IC50 of 0.5 nM in enzymatic assays. Against a panel of 384 kinases, BMS-986142 is highly selective, with only five other kinases (Tec, ITK, BLK, Txk, BMX) inhibited with 10,000 nM for both). When Ramos B cells are treated with anti-IgM to activate BCR, BMS-986142 inhibits BTK-dependent calcium flux with an IC50 of 9 nM[2].

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].

[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.

Chemical Properties

Cas No. 1643368-58-4 SDF
Canonical SMILES O=C1C2=C(C(F)=CC=C2)N(C)C(N1C3=C(C)[C@]([C@]4=C(F)C=C(C(N)=O)C5=C4C6=C(C[C@@H](C(C)(C)O)CC6)N5)=CC=C3)=O
Formula C32H30F2N4O4 M.Wt 572.6
Solubility DMSO : 125 mg/mL (218.30 mM);Water : < 0.1 mg/mL (insoluble) Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 1.7464 mL 8.7321 mL 17.4642 mL
5 mM 0.3493 mL 1.7464 mL 3.4928 mL
10 mM 0.1746 mL 0.8732 mL 1.7464 mL
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Average Rating: 5 ★★★★★ (Based on Reviews and 19 reference(s) in Google Scholar.)

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