BMS-986260   Click here for help

GtoPdb Ligand ID: 10662

Synonyms: BMS986260 | compound 10 [Velaparthi et al., 2020] | Example 32' [WO2016140884A1]
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: BMS-986260 is a potent, selective and orally bioavailable TGFβR1 inhibitor, that was developed for immuno-oncology potential [1]. The chemical structure of BMS-986260 is one of those claimed in patent WO2016140884A1 (Rigel Pharmaceuticals/Bristol-Myers Squibb). The PubChem CID match was obtained using the SMILES for BMS-986260 that was generated from the structure image presented in [1].
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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
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 CDK toolkit. 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 4
Topological polar surface area 92.03
Molecular weight 382.07
XLogP 3.21
No. Lipinski's rules broken 0
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.

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Canonical SMILES OCCn1cnc(c1c1ccc2n(n1)c(C#N)cn2)c1ccc(c(c1)Cl)F
Isomeric SMILES OCCn1cnc(c1c1ccc2n(n1)c(C#N)cn2)c1ccc(c(c1)Cl)F
InChI InChI=1S/C18H12ClFN6O/c19-13-7-11(1-2-14(13)20)17-18(25(5-6-27)10-23-17)15-3-4-16-22-9-12(8-21)26(16)24-15/h1-4,7,9-10,27H,5-6H2
InChI Key VZZBCNXVZFAIQX-UHFFFAOYSA-N
Bioactivity Comments
BMS-986260 potently inhibits human and mouse TGFβR1 in biochemical assays, and it is highly selective for TGFβR1 over TGFβR2 [1]. It modulates target-mediated responses in multiple TGFβ-dependent cellular assays, and produces therapeutic efficacy in combination with anti-PD-1 antibody in murine colorectal cancer (CRC) models.
Cardiovascular (CV) toxicities from TGFβR1 inhibition were alleviated in preclinical models, using an intermittent dosing regimen (3 days on and 4 days off). This regimen did not diminish the efficacy achieved with once daily dosing.
Potential off-targets (IC50 values <1 μM in a HTRF kinome screen) that are not included in the interactions table include TNIK, MINK (MINK1), HGK (MAP4K4), CK1δ (CSNK1D), CK1ε (CSNK1E), and KDR (VEGFR2).
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
transforming growth factor beta receptor 1 Hs Inhibitor Inhibition 8.8 pIC50 - 1
⤷ pIC50 8.8 (IC50 1.6x10-9 M) [1]
activin A receptor type 1B Hs Inhibitor Inhibition 7.5 pIC50 - 1
⤷ pIC50 7.5 (IC50 3.33x10-8 M) [1]
activin A receptor type 1 Hs Inhibitor Inhibition 7.2 pIC50 - 1
⤷ pIC50 7.2 (IC50 7.04x10-8 M) [1]