CCT241161   Click here for help

GtoPdb Ligand ID: 9814

Compound class: Synthetic organic
Comment: CCT241161 is an orally active pan RAF inhibitor that also inhibits SRC family kinases [1]. It was designed to show that the addition of SRC family kinase inhibition alongside RAF inhibition is able to circumvent the paradoxical SRC-mediated re-activation of the RAF-MAP kinase pathway that is observed in tumours with acquired resistance to RAF inhibitors. CCT241161 is marginally more potent in vitro than the analogue CCT196969 [1].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 3
Rotatable bonds 9
Topological polar surface area 151.6
Molecular weight 541.19
XLogP 4.21
No. Lipinski's rules broken 0
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Canonical SMILES CSc1cc(ccc1NC(=O)Nc1cc(nn1c1ccccc1)C(C)(C)C)Oc1ccnc2c1ncc(=O)[nH]2
Isomeric SMILES CSc1cc(ccc1NC(=O)Nc1cc(nn1c1ccccc1)C(C)(C)C)Oc1ccnc2c1ncc(=O)[nH]2
InChI InChI=1S/C28H27N7O3S/c1-28(2,3)22-15-23(35(34-22)17-8-6-5-7-9-17)32-27(37)31-19-11-10-18(14-21(19)39-4)38-20-12-13-29-26-25(20)30-16-24(36)33-26/h5-16H,1-4H3,(H,29,33,36)(H2,31,32,37)
Bioactivity Comments
CCT241161 has an anti-proliferative effect against patient-derived xenografts from tumours with acquired and intrinsic resistance to the BRAF inhibitor vemurafenib, and against those with acquired resistance to dabrafenib (a BRAFV600E inhibitor) plus trametinib (a MAPK inhibitor) [1].
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
LCK proto-oncogene, Src family tyrosine kinase Hs Inhibitor Inhibition 8.5 pIC50 - 1
pIC50 8.5 (IC50 3x10-9 M) [1]
Raf-1 proto-oncogene, serine/threonine kinase Hs Inhibitor Inhibition 8.2 pIC50 - 1
pIC50 8.2 (IC50 6x10-9 M) [1]
SRC proto-oncogene, non-receptor tyrosine kinase Hs Inhibitor Inhibition 8.0 pIC50 - 1
pIC50 8.0 (IC50 1x10-8 M) [1]
B-Raf proto-oncogene, serine/threonine kinase Hs Inhibitor Inhibition 7.5 pIC50 - 1
pIC50 7.5 (IC50 3x10-8 M) [1]