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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2D Structure
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Physico-chemical Properties
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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
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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
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]