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].
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
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
Click here for help
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)
No information available.
Summary of Clinical Use Click here for help
CEP-32496 is being assessed in Phase 1 clinical trial NCT01877811 for melanoma and metastatic colorectal cancer.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
The constitutively activating RAF mutation BRAFV600E is frequently found in human tumors and causes over-activation of the RAF/MEK/ERK signaling pathway that regulates cellular proliferation and survival. CEP-32496 inhibits this abberant activation and may result in a decrease in the proliferation of tumor cells expressing the mutated B-raf gene.