1. Protein Tyrosine Kinase/RTK
  2. Btk

BMS-986142 

Cat. No.: HY-101856
Handling Instructions

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

For research use only. We do not sell to patients.

BMS-986142 Chemical Structure

BMS-986142 Chemical Structure

CAS No. : 1643368-58-4

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  • Biological Activity

  • Protocol

  • Technical Information

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  • References

Description

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

IC50 & Target

IC50: 0.5 nM (BTK), 10 nM (TEC), 15 nM (ITK), 23 nM (BLK), 28 nM (TXK), 32 nM (BMX), 71 nM (LCK), 1100 nM (SRC) [1].

In Vitro

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 <100-fold selectivity for BTK. Four of these kinases are Tec family kinases, of which BTK is a member, and only Tec (IC50=10 nM) is inhibited with <30-fold selectivity compared with BTK. BMS-986142 does not inhibit CD40L-induced expression of CD86 or CD69 on peripheral blood B cells (IC50>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].

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].

Clinical Trial
Solvent & Solubility
In Vitro: 

10 mM in DMSO

Preparing
Stock Solutions
Concentration Solvent Mass 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
*Please refer to the solubility information to select the appropriate solvent.
References
Animal Administration
[2]

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

572.60

Formula

C₃₂H₃₀F₂N₄O₄

CAS No.

1643368-58-4

SMILES

O=C1C2=C(C(F)=CC=C2)N(C)C(N1C3=C(C)[[email protected]]([[email protected]]4=C(F)C=C(C(N)=O)C5=C4C6=C(C[[email protected]@H](C(C)(C)O)CC6)N5)=CC=C3)=O

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Shipping

Room temperature in continental US; may vary elsewhere

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Product Name:
BMS-986142
Cat. No.:
HY-101856
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BMS-986142

Cat. No.: HY-101856