agerafenib   Click here for help

GtoPdb Ligand ID: 7880

Synonyms: AC013773 | CEP 32496 | CEP-32496 | CEP32496 | RXDX-105
Compound class: Synthetic organic
Comment: The discovery and synthesis of agerafenib (CEP-32496) is described in [2] where it is compound 40. Agerafenib is an orally bioavailable B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor with potential antineoplastic activity, which selectively inhibits the activity of the mutated form (V600E) of BRAF kinase [1-2].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 10
Topological polar surface area 120.63
Molecular weight 517.16
XLogP 4.35
No. Lipinski's rules broken 0
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Canonical SMILES COc1cc2c(ncnc2cc1OC)Oc1cccc(c1)NC(=O)Nc1noc(c1)C(C(F)(F)F)(C)C
Isomeric SMILES COc1cc2c(ncnc2cc1OC)Oc1cccc(c1)NC(=O)Nc1noc(c1)C(C(F)(F)F)(C)C
InChI InChI=1S/C24H22F3N5O5/c1-23(2,24(25,26)27)19-11-20(32-37-19)31-22(33)30-13-6-5-7-14(8-13)36-21-15-9-17(34-3)18(35-4)10-16(15)28-12-29-21/h5-12H,1-4H3,(H2,30,31,32,33)
Bioactivity Comments
In vitro, CEP-32496 inhibits BRAFV600E-induced MEK phosphorylation with an IC50 of 82nM [2]. Additional targets for CEP-32496 include c-KIT, LCK, PDGRFβ, RET and Abl kinases, with Kd values of 2-3nM [2].
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
B-Raf proto-oncogene, serine/threonine kinase Hs Inhibitor Inhibition 7.4 pKd - 2
pKd 7.4 (Kd 3.6x10-8 M) [2]
Description: Inhibition of wild type BRAF activity.
Raf-1 proto-oncogene, serine/threonine kinase Hs Inhibitor Inhibition 7.4 pKd - 2
pKd 7.4 (Kd 3.9x10-8 M) [2]