Defactinib

Defactinib (INN, codenamed VS-6063) is an inhibitor of PTK2, also known as focal adhesion kinase (FAK), Pyk2, and MELK which was developed by Pfizer and licensed to Verastem Oncology as a potential treatment for solid tumors.

Defactinib

Skeletal formula and ball-and-stick model of defactinib
Clinical data
Other names	PF-04554878, VS-6063
Identifiers
IUPAC name N-methyl-4-[[4-[[3-[methyl(methylsulfonyl)amino]pyrazin-2-yl]methylamino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide
CAS Number	1073154-85-4
PubChem CID	25117126
DrugBank	DB12282
ChemSpider	32695161
UNII	53O87HA2QU
KEGG	D10618
ChEMBL	ChEMBL3137331
PDB ligand	7KD (PDBe, RCSB PDB)
CompTox Dashboard (EPA)	DTXSID901025937
Chemical and physical data
Formula	C20H21F3N8O3S
Molar mass	510.50 g·mol−1
3D model (JSmol)	Interactive image
SMILES CNC(=O)C1=CC=C(C=C1)NC2=NC=C(C(=N2)NCC3=NC=CN=C3N(C)S(=O)(=O)C)C(F)(F)F
InChI InChI=1S/C20H21F3N8O3S/c1-24-18(32)12-4-6-13(7-5-12)29-19-28-10-14(20(21,22)23)16(30-19)27-11-15-17(26-9-8-25-15)31(2)35(3,33)34/h4-10H,11H2,1-3H3,(H,24,32)(H2,27,28,29,30) Key:FWLMVFUGMHIOAA-UHFFFAOYSA-N

Development for mesothelioma was discontinued in 2015 due to lack of efficacy in a placebo-controlled phase II trial.^[1][2] Subsequent research in patients with specific NF2 mutations also found limited activity.^[3]

The co-packaged medication avutometinib/defactinib was approved for medical use in the United States in May 2025.^[4][5]