product name FRAX597
Description: FRAX597 is a potent, ATP-competitive inhibitor of group I PAKs with IC50 of 8 nM, 13 nM, and 19 nM for PAK1, PAK2, and PAK3, respectively. FRAX597 inhibits tumorigenesis of neurofibromatosis type 2 (NF2)-associated Schwannomas. FRAX597 inhibits the proliferation of NF2-deficient schwannoma cells in culture and displayed potent anti-tumor activity in vivo, impairing schwannoma development in an orthotopic model of NF2. These studies identify a novel class of orally available ATP-competitive Group I PAK inhibitors with significant potential for the treatment of NF2 and other cancers.
References: J Biol Chem. 2013 Oct 4;288(40):29105-14; Cancer Res. 2012 Nov 15;72(22):5966-75.
558.10
Formula
C29H28ClN7OS
CAS No.
1286739-19-2
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 14 mg/mL (25.1 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: FRAX597 (100 n M) displays a significant inhibitory capacity toward YES1 (87%), RET (82%), CSF1R (91%), TEK (87%), PAK1 (82%), and PAK2 (93%), while displays minimal inhibitory activity towards the group II PAKs: PAK4 (0%), PAK6 (23%), and PAK7 (8%). FRAX597 treatment dramatically impairs the proliferation of Nf2-null SC4 Schwann cells (SC4 cells). FRAX597 displays an IC50 value of 48 nM against wild type PAK1, while IC 50 values against the V342F and V342Y PAK1 mutants are higher than 3μM and 2 μM, respectively. FRAX597 inhibits the proliferation and motility of both benign (Ben-Men1, 3μM) and malignant (KT21-MG1, 0.4 μM) meningiomas cells after treating of 72 h. Kinase Assay: IC50 values are determined using a 10 concentration point, non-radioactive, functional assay that employs a fluorescence-based, coupled-enzyme format, according to the manufacturer’s protocol (Z’-LYTE@biochemical assay). Kinase selectivity is determined using both the Z’-LYTE@ and Adapta@ kinase assay format. Cell Assay: 30,000 cells/well are plated in 12-well dishes in triplicate. Cell growth media with or without FRAX597 is replaced daily. At indicated time points, cells from individual wells are trypsinized and counted using a Coulter counter. |
|---|---|
| In Vivo | 30,000 cells/well are plated in 12-well dishes in triplicate. Cell growth media with or without FRAX597 is replaced daily. At indicated time points, cells from individual wells are trypsinized and counted using a Coulter counter. |
| Animal model | SCID mice with orthotopic meningioma model |
| Formulation & Dosage | Dissolved in 10% (PEG400:Tween-80:PVP-K30, 90:5:5), 15% Vitamin E-TPGS, 75% of hydroxypropylcellulose (0.5%) in 50 mM citrate buffer (pH 3.0); 90 mg/kg/day; p.o. administration |
| References | J Biol Chem. 2013 Oct 4;288(40):29105-14; Cancer Res. 2012 Nov 15;72(22):5966-75. |
