CCT196969   Click here for help

GtoPdb Ligand ID: 9815

Compound class: Synthetic organic
Comment: CCT196969 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.
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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 8
Topological polar surface area 126.3
Molecular weight 513.19
XLogP 3.63
No. Lipinski's rules broken 0
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Canonical SMILES O=C(Nc1cc(nn1c1ccccc1)C(C)(C)C)Nc1ccc(cc1F)Oc1ccnc2c1ncc(=O)[nH]2
Isomeric SMILES O=C(Nc1cc(nn1c1ccccc1)C(C)(C)C)Nc1ccc(cc1F)Oc1ccnc2c1ncc(=O)[nH]2
InChI InChI=1S/C27H24FN7O3/c1-27(2,3)21-14-22(35(34-21)16-7-5-4-6-8-16)32-26(37)31-19-10-9-17(13-18(19)28)38-20-11-12-29-25-24(20)30-15-23(36)33-25/h4-15H,1-3H3,(H,29,33,36)(H2,31,32,37)
Bioactivity Comments
CCT196969 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
Raf-1 proto-oncogene, serine/threonine kinase Hs Inhibitor Inhibition 8.0 pIC50 - 1
pIC50 8.0 (IC50 1x10-8 M) [1]
LCK proto-oncogene, Src family tyrosine kinase Hs Inhibitor Inhibition 7.7 pIC50 - 1
pIC50 7.7 (IC50 2x10-8 M) [1]
SRC proto-oncogene, non-receptor tyrosine kinase Hs Inhibitor Inhibition 7.5 pIC50 - 1
pIC50 7.5 (IC50 3x10-8 M) [1]
B-Raf proto-oncogene, serine/threonine kinase Hs Inhibitor Inhibition 7.0 pIC50 - 1
pIC50 7.0 (IC50 1x10-7 M) [1]