1286739-19-2
1286739-19-2 structure
- Name: FRAX 597
- Chemical Name: 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,hydrochloride
- CAS Number: 1286739-19-2
- Molecular Formula: C29H28ClN7OS
- Molecular Weight: 558.10
- Catalog: Biochemical Inhibitor Cytoskeletal Signaling PAK inhibitor
- Create Date: 2016-06-03 00:06:51
- Modify Date: 2024-01-06 08:59:23
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FRAX597 is a potent group I p21-activated Kinases (PAKs) inhibitor with IC50 of 8, 13 and 19 nM for PAK1, 2 and 3.
| Name | 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,hydrochloride |
|---|---|
| Synonyms |
6-[2-Chloro-4-(1,3-thiazol-5-yl)phenyl]-8-ethyl-2-{[4-(4-methyl-1-piperazinyl)phenyl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one hydrochloride (1:1)
frax597 Pyrido[2,3-d]pyrimidin-7(8H)-one, 6-[2-chloro-4-(5-thiazolyl)phenyl]-8-ethyl-2-[[4-(4-methyl-1-piperazinyl)phenyl]amino]-, hydrochloride (1:1) 6-(2-Chloro-4-thiazol-5-yl-phenyl)-8-ethyl-2-[4-(4-Methyl-piperazin-1-yl)-phenylaMino]-8H-pyrido[2,3-d]pyriMidin-7-one FRAX 597 |
| Description | FRAX597 is a potent group I p21-activated Kinases (PAKs) inhibitor with IC50 of 8, 13 and 19 nM for PAK1, 2 and 3. |
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| Related Catalog | |
| Target |
PAK1:8 nM (IC50) PAK2:13 nM (IC50) PAK3:19 nM (IC50) |
| In Vitro | 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]. |
| In Vivo | 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 (0.55 g versus 1.87 g, p=0.0001)[1]. |
| Cell Assay | 30,000 SC4 cells/well are plated in 12-well dishes in triplicate. Cell growth media with or without FRAX597 (1 μM) is replaced daily. At indicated time points, cells from individual wells are trypsinized and counted using a Coulter counter. Statistical analysis is performed using a Student's t test. For cell cycle analysis, cells are harvested, washed once with PBS and fixed in cold 70% ethanol. Fixed cells are resuspended in propidium iodide (PI) buffer (50 μg/mL PI, 250 mg/mL RNase A in PBS) and incubated overnight at 4°C in the dark. Cell cycle distribution is evaluated using Coulter Epics XL flow cytometer. Data are analyzed using WinMDI software[1]. |
| Animal Admin | Mice[1] Nf2-/- SC4 Schwann cells are transduced by lentiviruses carrying pLuc-mCherry and sorted by FACS. 5×104 cells are transplanted into the sciatic nerve sheath of NOD/SCID mice (8 weeks of age) by intraneural injection. Tumor progression is monitored weekly by bioluminescence imaging (BLI) on an IVIS-200 system. The representative images from bioluminescence imaging (BLI) of mice carrying orthotopic tumors treated with FRAX597 (100 mg/kg) or vehicle control at day 14 of treatment. NOD/SCID mice are injected intraneurally with 5×104 SC4/pLuc-mCherry cells and are enrolled into treatment after 10 days. Mice are treated daily for 14 days and imaged every 3 days to follow tumor development. |
| References |
| Molecular Formula | C29H28ClN7OS |
|---|---|
| Molecular Weight | 558.10 |
| PSA | 110.65000 |
| LogP | 5.97750 |
| Storage condition | -20℃ |