Synonym
BMS-935177; BMS 935177; BMS935177.
IUPAC/Chemical Name
7-(2-hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide
InChi Key
TVJRDCQUZMGBAB-UHFFFAOYSA-N
InChi Code
InChI=1S/C31H26N4O3/c1-17-19(8-6-10-26(17)35-16-33-24-9-5-4-7-22(24)30(35)37)20-13-14-23(29(32)36)28-27(20)21-12-11-18(31(2,3)38)15-25(21)34-28/h4-16,34,38H,1-3H3,(H2,32,36)
SMILES Code
O=C(C1=CC=C(C2=CC=CC(N3C(C4=C(C=CC=C4)N=C3)=O)=C2C)C5=C1NC6=C5C=CC(C(C)(O)C)=C6)N
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
Bruton’s tyrosine kinase (BTK) belongs to the TEC family of nonreceptor tyrosine kinases and plays a critical role in multiple cell types responsible for numerous autoimmune diseases.
Biological target:
BMS-935177 is a potent and selective reversible inhibitor of Bruton’s tyrosine kinase (Btk) with an IC50 of 3 nM.
In vitro activity:
Compound 6 (BMS-935177) (inhibited calcium flux in human Ramos B cells (IC50 = 27 nM) and inhibited CD69 surface expression in peripheral B cells stimulated with anti-IgM and anti-IgG.
Reference: J Med Chem. 2016 Sep 8;59(17):7915-35. https://pubmed.ncbi.nlm.nih.gov/27531604/
In vivo activity:
In the KLH assay, 6 (BMS-935177) (showed superior in vivo potency compared to 14. As shown in Figure 5A, when dosed orally once daily at 5, 20, and 45 mg/kg to mice, the compound inhibited anti-KLH antibodies of the IgG isotype at day 14, with statistically significant reductions at all doses.
Reference: J Med Chem. 2016 Sep 8;59(17):7915-35. https://pubmed.ncbi.nlm.nih.gov/27531604/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
115.0 |
228.82 |
|
| Ethanol |
100.0 |
198.98 |
|
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
502.57
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. De Lucca GV, Shi Q, Liu Q, Batt DG, Beaudoin Bertrand M, Rampulla R, Mathur A, Discenza L, D'Arienzo C, Dai J, Obermeier M, Vickery R, Zhang Y, Yang Z, Marathe P, Tebben AJ, Muckelbauer JK, Chang CJ, Zhang H, Gillooly K, Taylor T, Pattoli MA, Skala S, Kukral DW, McIntyre KW, Salter-Cid L, Fura A, Burke JR, Barrish JC, Carter PH, Tino JA. Small Molecule Reversible Inhibitors of Bruton's Tyrosine Kinase (BTK): Structure-Activity Relationships Leading to the Identification of 7-(2-Hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide (BMS-935177). J Med Chem. 2016 Sep 8;59(17):7915-35. doi: 10.1021/acs.jmedchem.6b00722. Epub 2016 Aug 26. PMID: 27531604.
In vitro protocol:
1. De Lucca GV, Shi Q, Liu Q, Batt DG, Beaudoin Bertrand M, Rampulla R, Mathur A, Discenza L, D'Arienzo C, Dai J, Obermeier M, Vickery R, Zhang Y, Yang Z, Marathe P, Tebben AJ, Muckelbauer JK, Chang CJ, Zhang H, Gillooly K, Taylor T, Pattoli MA, Skala S, Kukral DW, McIntyre KW, Salter-Cid L, Fura A, Burke JR, Barrish JC, Carter PH, Tino JA. Small Molecule Reversible Inhibitors of Bruton's Tyrosine Kinase (BTK): Structure-Activity Relationships Leading to the Identification of 7-(2-Hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide (BMS-935177). J Med Chem. 2016 Sep 8;59(17):7915-35. doi: 10.1021/acs.jmedchem.6b00722. Epub 2016 Aug 26. PMID: 27531604.
In vivo protocol:
1. De Lucca GV, Shi Q, Liu Q, Batt DG, Beaudoin Bertrand M, Rampulla R, Mathur A, Discenza L, D'Arienzo C, Dai J, Obermeier M, Vickery R, Zhang Y, Yang Z, Marathe P, Tebben AJ, Muckelbauer JK, Chang CJ, Zhang H, Gillooly K, Taylor T, Pattoli MA, Skala S, Kukral DW, McIntyre KW, Salter-Cid L, Fura A, Burke JR, Barrish JC, Carter PH, Tino JA. Small Molecule Reversible Inhibitors of Bruton's Tyrosine Kinase (BTK): Structure-Activity Relationships Leading to the Identification of 7-(2-Hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide (BMS-935177). J Med Chem. 2016 Sep 8;59(17):7915-35. doi: 10.1021/acs.jmedchem.6b00722. Epub 2016 Aug 26. PMID: 27531604.
Small Molecule Reversible Inhibitors of Bruton’s Tyrosine Kinase (BTK): Structure–Activity Relationships Leading to the Identification of 7-(2-Hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide (BMS-935177)
George V. De Lucca, Qing Shi, Qingjie Liu, Douglas G. Batt, Myra Beaudoin Bertrand, Rick Rampulla, Arvind Mathur, Lorell Discenza, Celia D’Arienzo, Jun Dai, Mary Obermeier, Rodney Vickery, Yingru Zhang, Zheng Yang, Punit Marathe, Andrew J. Tebben, Jodi K. Muckelbauer, ChiehYing J. Chang, Huiping Zhang, Kathleen Gillooly, Tracy Taylor, Mark A. Pattoli, Stacey Skala, Daniel W. Kukral, Kim W. McIntyre, Luisa Salter-Cid, Aberra Fura, James R. Burke, Joel C. Barrish, Percy H. Carter, and Joseph A. Tino
Publication Date (Web): August 17, 2016 (Article)
DOI: 10.1021/acs.jmedchem.6b00722
