defactinib

{{Short description|Pharmaceutical}}

{{Use dmy dates|date=May 2025}}

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| image2 = Defactinib ball-and-stick 5MAH.png

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| caption = Skeletal formula and ball-and-stick model of defactinib

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| CAS_number = 1073154-85-4

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| PubChem = 25117126

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| DrugBank = DB12282

| ChemSpiderID = 32695161

| UNII = 53O87HA2QU

| KEGG = D10618

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| ChEMBL = 3137331

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| PDB_ligand = 7KD

| synonyms = PF-04554878, VS-6063

| IUPAC_name = N-methyl-4-[[4-[[3-[methyl(methylsulfonyl)amino]pyrazin-2-yl]methylamino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide

| C=20 | H=21 | F=3 | N=8 | O=3 | S=1

| 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

| StdInChI = 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)

| StdInChIKey = FWLMVFUGMHIOAA-UHFFFAOYSA-N

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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.

Development for mesothelioma was discontinued in 2015 due to lack of efficacy in a placebo-controlled phase II trial.{{cite press release |url=https://www.reuters.com/article/us-verastem-study-idUSKCN0RS1DR20150928 |title=Verastem stops cancer therapy development; shares plunge | vauthors = Nathan VL |publisher=Reuters |date=28 September 2015 |access-date=5 June 2022}}{{cite journal | vauthors = Fennell DA, Baas P, Taylor P, Nowak AK, Gilligan D, Nakano T, Pachter JA, Weaver DT, Scherpereel A, Pavlakis N, van Meerbeeck JP, Cedrés S, Nolan L, Kindler H, Aerts JG | display-authors = 6 | title = Maintenance Defactinib Versus Placebo After First-Line Chemotherapy in Patients With Merlin-Stratified Pleural Mesothelioma: COMMAND-A Double-Blind, Randomized, Phase II Study | journal = Journal of Clinical Oncology | volume = 37 | issue = 10 | pages = 790–798 | date = April 2019 | pmid = 30785827 | doi = 10.1200/JCO.2018.79.0543 | s2cid = 73478275 }} Subsequent research in patients with specific NF2 mutations also found limited activity.{{cite journal | vauthors = Jackman DM, Jegede O, Zauderer MG, Mitchell EP, Zwiebel J, Gray RJ, Li S, McShane L, Rubinstein L, Patton DR, Williams PM | display-authors = 6 | title=A phase 2 study of defactinib (VS-6063) in patients with NF2 altered tumors: Results from NCI-match (EAY131) subprotocol U. | journal=Journal of Clinical Oncology | publisher=American Society of Clinical Oncology (ASCO) | volume=39 | issue=15_suppl | date=20 May 2021 | issn=0732-183X | doi=10.1200/jco.2021.39.15_suppl.3087 | pages=3087| s2cid = 236401789 }}

The co-packaged medication avutometinib/defactinib was approved for medical use in the United States in May 2025.{{cite web | title=FDA grants accelerated approval to the combination of avutometinib and defactinib for KRAS-mutated recurrent low-grade serous ovarian cancer | website=U.S. Food and Drug Administration | date=8 May 2025 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-combination-avutometinib-and-defactinib-kras-mutated-recurrent-low | archive-url=https://web.archive.org/web/20250508225200/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-combination-avutometinib-and-defactinib-kras-mutated-recurrent-low | url-status=dead | archive-date=8 May 2025 | access-date=16 May 2025}} {{PD-notice}}{{cite press release | title=FDA Approves the Avmapki Fakzynja Combination Therapy as the First-Ever Treatment for Adult Patients with KRAS-mutated Recurrent Low-Grade Serous Ovarian Cancer | website=Verastem | url=https://investor.verastem.com/news-releases/news-release-details/fda-approves-avmapkitm-fakzynjatm-combination-therapy-first-ever | access-date=16 May 2025}}