FRAX597

• CAT Number: I001119
• CAS Number: 1286739-19-2
• Molecular Formula: C29H28ClN7OS
• Molecular Weight: 558.10
• Purity: ≥95%
• Synonyms: 6-[2-chloro-4-(1,3-thiazol-5-yl)phenyl]-8-ethyl-2-[4-(4-methylpiperazin-1-yl)anilino]pyrido[2,3-d]pyrimidin-7-one
• InChI: InChI=1S/C29H28ClN7OS/c1-3-37-27-20(14-24(28(37)38)23-9-4-19(15-25(23)30)26-17-31-18-39-26)16-32-29(34-27)33-21-5-7-22(8-6-21)36-12-10-35(2)11-13-36/h4-9,14-18H,3,10-13H2,1-2H3,(H,32,33,34)
• InChIKey: DHUJCQOUWQMVCG-UHFFFAOYSA-N
• SMILES: CCN1C2=NC(=NC=C2C=C(C1=O)C3=C(C=C(C=C3)C4=CN=CS4)Cl)NC5=CC=C(C=C5)N6CCN(CC6)C

FRAX597 is a potent group I p21-activated Kinases (PAKs) inhibitor with IC50 of 8, 13 and 19 nM for PAK1, 2 and 3.
FRAX597 is determined to be a potent, ATP-competitive inhibitor of group I PAKs (PAK 1-3), with biochemical IC50 values as follows: PAK1 IC50=8 nM, PAK2 IC50=13 nM, PAK3 IC50=19 nM. The IC50 toward PAK4, a member of group II PAKs is >10 μM. At a concentration of 100 nM FRAX597 displays a significant (>80% inhibition) inhibitory capacity toward YES1 (87%), RET (82%), CSF1R (91%), TEK (87%), PAK1 (82%), and PAK2 (93%). When measured using the Kinase Glo Assay in the presence of 20 nM protein and 1 μM ATP, FRAX597 displayed an IC50 value of 48 nM against wild type PAK1, while IC50 values against the V342F and V342Y PAK1 mutants are higher than 3 μM and 2 μM, respectively[1].
Analysis of the flux reading for the animals in the two cohorts demonstrates a significantly slower tumor growth rate in FRAX597-treated mice compared with control mice. After 14 days of treatment the animals are sacrificed and the tumors excised and weighed. FRAX597-treated cohort shows significantly lower average tumor weight compared with the control cohort [1].

Reference

[1]. Licciulli S, et al. FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of neurofibromatosis type 2 (NF2)-associated Schwannomas. J Biol Chem. 2013 Oct 4;288(40):29105-14.
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