BMS-986158   Click here for help

GtoPdb Ligand ID: 11757

Synonyms: BMS986158 | compound 18 [PMID: 34543572]
PDB Ligand
Compound class: Synthetic organic
Comment: BMS-986158 is a clinical candidate inhibitor of bromodomain and extra-terminal (BET) domain-containing proteins [3]. It was developed as a potential treatment for haematologic and solid tumours. Early pan-BET inhibitors include (+)-JQ1 and molibresib (GSK525762), but some tumours are either inherently resistant to these inhibitors [4], or develop treatment-induced resistance [1]. BMS-986158 was designed on a different chemical scaffold to combat resistance issues.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

BMS-986158 is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 77.99
Molecular weight 495.26
XLogP 4.99
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES Cc1nnn(c1c1cnc2c(c1)n([C@H](c1ccccc1)C1CCOCC1)c1c2ccc(c1)C(O)(C)C)C
Isomeric SMILES Cn1nnc(C)c1c1cnc2c(c1)n([C@@H](C1CCOCC1)c1ccccc1)c1c2ccc(c1)C(C)(C)O
InChI 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
InChI Key KGERZPVQIRYWRK-GDLZYMKVSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
BMS-986158 has been advanced to clinical evaluation.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03936465 Study of the Bromodomain (BRD) and Extra-Terminal Domain (BET) Inhibitor BMS-986158 in Pediatric Cancer Phase 1 Interventional Dana-Farber Cancer Institute
NCT04817007 A Study to Assess the Safety and Tolerability of BMS-986158 Alone and in Combination With Either Ruxolitinib or Fedratinib in Participants With Blood Cancer (Myelofibrosis) Phase 1 Interventional Bristol-Myers Squibb
NCT02419417 Study of BMS-986158 in Subjects With Select Advanced Cancers Phase 1/Phase 2 Interventional Bristol-Myers Squibb