KPT-9274

KPT-9274 is a selective and orally bioavailable allosteric inhibitor of PAK4 . P21 protein (Cdc42/Rac)-activated kinase 4 (PAK4) is a serine/threonine-protein kinase and a member of the PAK family of proteins which are Rac1 and Cdc42 effectors. PAK4 is a mediator of filopodia formation and stabilizes β-catenin transcriptional activity, and is involved in disease progression for several solid tumors . KPT-9274 is a selective and orally bioavailable PAK4 inhibitor. In MDA-MB-468 cells, KPT-9274 showed anti-tumor activity with IC50 value of 0.12 μM. KPT-9274 reduced PAK4 protein and the key downstream effectors of cell cycle (β-catenin, cyclin D1), cell migration (cofilin), autophagy (AMPK) and apoptosis (Caspase and PARP cleavage) . In RCC cells, KPT-9274 dose-dependently inhibited cell viability . In AML cell lines, KPT-9274 (1 nM-10 μM) inhibited cell proliferation in a dose-and time- dependent way and reduced protein and mRNA expression of PAK4 . In mice inoculated with MDA-MB-231 or MDA-MB-468 cells, KPT-9274 were given orally once daily (5 or 7 days/week) without major toxicity. KPT-9274 induced a maximum TGI of ~55% and ~70% in MDA-MB-231 and MDA-MB-468 mice, respectively . In subcutaneous xenograft mouse models, KPT-9274 inhibited RCC growth . In human AML leukemia xenograft model, KPT-9274 (150 mg/kg) significantly inhibited tumor growth, prevented invasion of MV4-11 cells, and improved overall survival .

Product information

CAS Number: 1643913-93-2

Molecular Weight: 610.62

Formula: C35H29F3N4O3

Chemical Name: (Z,2E)-3-(6-aminopyridin-2-yl)-N-({5-[4-(4,4-difluoropiperidine-1-carbonyl)phenyl]-7-(4-fluorophenyl)-1-benzofuran-2-yl}methyl)prop-2-enimidic acid

Smiles: NC1=CC=CC(/C=C/C(/O)=N/CC2=CC3C=C(C=C(C4=CC=C(F)C=C4)C=3O2)C2C=CC(=CC=2)C(=O)N2CCC(F)(F)CC2)=N1

InChiKey: KXGUHCDGIDAEIP-OUKQBFOZSA-N

InChi: InChI=1S/C35H29F3N4O3/c36-27-10-8-23(9-11-27)30-20-25(22-4-6-24(7-5-22)34(44)42-16-14-35(37,38)15-17-42)18-26-19-29(45-33(26)30)21-40-32(43)13-12-28-2-1-3-31(39)41-28/h1-13,18-20H,14-17,21H2,(H2,39,41)(H,40,43)/b13-12+

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

Products are for research use only. Not for human use.