BMS-986158 (BMS986158; BMS 986158) is a novel, potent and selective BET (bromodomain and extra-terminal) protein inhibitor with potential antineoplastic activity. BET proteins (BRD2, BRD3, BRD4 and BRDT) are transcriptional regulators that bind to acetylated lysines on the tails of histones H3 and H4, and regulate chromatin structure and function; they play an important role in the modulation of gene expression during development and cellular growth. As a BET inhibitor, BMS-986158 acts by binding to the acetyl-lysine binding site in the BRD of BET proteins, thereby preventing the interaction between BET proteins and acetylated histones, which disrupts chromatin remodeling and prevents the expression of certain growth-promoting genes, resulting in an inhibition of tumor cell growth.
Physicochemical Properties
| Molecular Formula | C30H33N5O2 |
| Molecular Weight | 495.61532664299 |
| Exact Mass | 495.263 |
| CAS # | 1800340-40-2 |
| PubChem CID | 118196485 |
| Appearance | White to off-white solid powder |
| LogP | 4.1 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 37 |
| Complexity | 769 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | OC(C)(C)C1=CC=C2C(N([C@H](C3=CC=CC=C3)C4CCOCC4)C5=C2N=CC(C6=C(C)N=NN6C)=C5)=C1 |
| InChi Key | KGERZPVQIRYWRK-GDLZYMKVSA-N |
| InChi Code | InChI=1S/C30H33N5O2/c1-19-28(34(4)33-32-19)22-16-26-27(31-18-22)24-11-10-23(30(2,3)36)17-25(24)35(26)29(20-8-6-5-7-9-20)21-12-14-37-15-13-21/h5-11,16-18,21,29,36H,12-15H2,1-4H3/t29-/m1/s1 |
| Chemical Name | (S)-2-(3-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-5-(phenyl(tetrahydro-2H-pyran-4-yl)methyl)-5H-pyrido[3,2-b]indol-7-yl)propan-2-ol |
| Synonyms | BMS-986158; BMS 986158; BMS986158 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | BMS-986158 exhibits potential anti-tumor efficacy as an inhibitor of the ecto-terminal domain (BET) and bromodomain (BRD) protein families. Following injection, the BET inhibitor BMS-986158 binds to the BET protein BRD's acetyl lysine binding site, blocking the BET protein's ability to interact with acetylated histones. Tumor cell development is inhibited as a result of this disruption of chromatin remodeling and suppression of the expression of several growth-promoting genes [2]. |
| References |
[1]. Potent BRD4 inhibitor suppresses cancer cell-macrophage interaction. Nat Commun. 2020 Apr 14;11(1):1833. |
| Additional Infomation |
BMS-986158 is under investigation in clinical trial NCT02419417 (Study of BMS-986158 in Subjects With Select Advanced Cancers). Ezobresib is an inhibitor of the Bromodomain (BRD) and Extra-Terminal domain (BET) family of proteins, with potential antineoplastic activity. Upon administration, ezobresib binds to the acetyl-lysine binding site in the BRD of BET proteins, thereby preventing the interaction between BET proteins and acetylated histones. This disrupts chromatin remodeling and prevents the expression of certain growth-promoting genes, resulting in an inhibition of tumor cell growth. BET proteins (BRD2, BRD3, BRD4 and BRDT) are transcriptional regulators that bind to acetylated lysines on the tails of histones H3 and H4, and regulate chromatin structure and function; they play an important role in the modulation of gene expression during development and cellular growth. |
Solubility Data
| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~100.88 mM) H2O : < 0.1 mg/mL |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.04 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.04 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.04 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0177 mL | 10.0884 mL | 20.1767 mL | |
| 5 mM | 0.4035 mL | 2.0177 mL | 4.0353 mL | |
| 10 mM | 0.2018 mL | 1.0088 mL | 2.0177 mL |