BMS-986142 | CAS#1643368-58-4 | BTK inhibitor

MedKoo Cat#: 206730 | Name: BMS-986142

Description:

WARNING: This product is for research use only, not for human or veterinary use.

BMS-986142 is a potent, selective, reversible BTK inhibitor. BMS-986142 shows BTK IC50 = 0.5nM; human WB IC50 = 90 nM. In molecule of BMS-986142, two atropisomeric centers were rotationally locked to provide a single, stable atropisomer, resulting in enhanced potency and selectivity as well as a reduction in safety liabilities. With significantly enhanced potency and selectivity, excellent in vivo properties and efficacy, and a very desirable tolerability and safety profile, BMS-986142 was advanced into clinical studies.

Chemical Structure

BMS-986142

CAS#1643368-58-4

Theoretical Analysis

MedKoo Cat#: 206730

Name: BMS-986142

CAS#: 1643368-58-4

Chemical Formula: C32H30F2N4O4

Exact Mass: 572.2235

Molecular Weight: 572.61

Elemental Analysis: C, 67.12; H, 5.28; F, 6.64; N, 9.78; O, 11.18

Price and Availability

Size	Price	Availability
5mg	USD 150.00	Ready to ship
10mg	USD 250.00	Ready to ship
25mg	USD 450.00	Ready to ship
50mg	USD 750.00	Ready to ship
100mg	USD 1,250.00	Ready to ship
200mg	USD 1,950.00	Ready to ship
500mg	USD 2,650.00	2 weeks
1g	USD 3,850.00	2 weeks
2g	USD 6,450.00	2 weeks

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Related CAS #

No Data

Synonym

BMS-986142; BMS 986142; BMS986142.

IUPAC/Chemical Name

(2S,5R,3S)-6-fluoro-5-(3-(8-fluoro-1-methyl-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl)-2-methylphenyl)-2-(2-hydroxypropan-2-yl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide

InChi Key

ZRYMMWAJAFUANM-INIZCTEOSA-N

InChi Code

InChI=1S/C32H30F2N4O4/c1-15-17(7-6-10-24(15)38-30(40)19-8-5-9-21(33)28(19)37(4)31(38)41)25-22(34)14-20(29(35)39)27-26(25)18-12-11-16(32(2,3)42)13-23(18)36-27/h5-10,14,16,36,42H,11-13H2,1-4H3,(H2,35,39)/t16-/m0/s1

SMILES Code

O=C(C1=CC(F)=[C@]([C@]2=CC=CC(N3C(N(C)C4=C(C=CC=C4F)C3=O)=O)=C2C)C5=C1NC6=C5CC[C@H](C(C)(O)C)C6)N

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C9R02B01

QC Data

View QC data: current batch, Lot#C9R02B01

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

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

In vitro activity:

Previous studies of BTK inhibition indicate that BTK is essential in FcγR-mediated inflammatory cytokine production. Therefore, this study investigated the effect of BMS-986142 on the ability of peripheral blood mononuclear cells to produce cytokines. BMS-986142 inhibited TNF-α and IL-6 production (IC50, 3 and 4 nM, respectively; Table 2) in these cells stimulated through IgG-containing IC-driven, low affinity-activating FcγR (FcγRIIa and FcγRIIIa). Potencies were equivalent to those measured against BCR-dependent functional endpoints in B cells. LPS stimulation of TNF-α in peripheral blood mononuclear cells was not inhibited by BMS-986142 (IC50, >30,000 nM), consistent with published reports showing TLR4 signaling is not dependent on BTK catalytic activity. Reference: PLoS One. 2017; 12(7): e0181782. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524405/

In vivo activity:

In this study, 14f (BMS-986142) was shown to block the increase in severe proteinuria (Figure 14A), a measure of the underlying nephritis. Treatment with 14f also provided protection from disease-related death over the course of the treatment (Figure 14B). Histological evaluation of the kidneys at the end of the study demonstrated that treatment with 14f provided robust protection against tubulo-interstitial and glomerular nephritis, as well as inflammatory infiltration, at levels equivalent to those seen with prednisolone (Figure 14C). IgG immune complex deposition, critical in driving disease pathobiology in both this murine model and human lupus nephritis, was prominent in the capillaries of the glomeruli of vehicle control mice. As seen in Figure 14D, histological evaluation revealed that 14f reduced the level of immune complex deposits as effectively as prednisolone. Reference: J Med Chem. 2016 Oct 13;59(19):9173-9200. https://pubmed.ncbi.nlm.nih.gov/27583770/

	Solvent	mg/mL	mM
Solubility
	DMSO	76.7	133.90
	DMSO:PBS (pH 7.2) (1:3)	0.3	0.44
	DMF	30.0	52.39
	Ethanol	15.0	26.20

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 572.61 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Gillooly KM, Pulicicchio C, Pattoli MA, Cheng L, Skala S, Heimrich EM, McIntyre KW, Taylor TL, Kukral DW, Dudhgaonkar S, Nagar J, Banas D, Watterson SH, Tino JA, Fura A, Burke JR. Bruton's tyrosine kinase inhibitor BMS-986142 in experimental models of rheumatoid arthritis enhances efficacy of agents representing clinical standard-of-care. PLoS One. 2017 Jul 24;12(7):e0181782. doi: 10.1371/journal.pone.0181782. PMID: 28742141; PMCID: PMC5524405. 2. Watterson SH, De Lucca GV, Shi Q, Langevine CM, Liu Q, Batt DG, Beaudoin Bertrand M, Gong H, Dai J, Yip S, Li P, Sun D, Wu DR, Wang C, Zhang Y, Traeger SC, Pattoli MA, Skala S, Cheng L, Obermeier MT, Vickery R, Discenza LN, D'Arienzo CJ, Zhang Y, Heimrich E, Gillooly KM, Taylor TL, Pulicicchio C, McIntyre KW, Galella MA, Tebben AJ, Muckelbauer JK, Chang C, Rampulla R, Mathur A, Salter-Cid L, Barrish JC, Carter PH, Fura A, Burke JR, Tino JA. 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. doi: 10.1021/acs.jmedchem.6b01088. Epub 2016 Sep 19. PMID: 27583770.

In vitro protocol:

In vivo protocol:

1: Watterson SH, De Lucca GV, Shi Q, Langevine CM, Liu Q, Batt DG, Beaudoin Bertrand M, Gong H, Dai J, Yip S, Li P, Sun D, Wu DR, Wang C, Zhang Y, Traeger SC, Pattoli MA, Skala S, Cheng L, Obermeier MT, Vickery R, Discenza LN, D'Arienzo CJ, Zhang Y, Heimrich E, Gillooly KM, Taylor TL, Pulicicchio C, McIntyre KW, Galella MA, Tebben AJ, Muckelbauer JK, Chang C, Rampulla R, Mathur A, Salter-Cid L, Barrish JC, Carter PH, Fura A, Burke JR, Tino JA. 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. PubMed PMID: 27583770.