PHA-665752

SKU: orb1301049

Description

PHA-665752 is a potent and selective ATP-competitive inhibitor of the c-Met receptor tyrosine kinase, exhibiting an IC50 of 9 nM. It demonstrates over 50-fold selectivity against other kinases. This compound is a valuable research tool for studying c-Met signaling in cancer models, both in cellular assays and in vivo studies.

Research Area

Metabolism Research

Key Properties

• CAS Number: 477575-56-7
• MW: 641.61
• Purity: 99.35% (May vary between batches)
• Formula: C₃₂H₃₄Cl₂N₄O₄S
• SMILES: C(=C\1/C=2C(NC1=O)=CC=C(S(CC3=C(Cl)C=CC=C3Cl)(=O)=O)C2)\C4=C(C)C(C(=O)N5[C@@H](CN6CCCC6)CCC5)=C(C)N4
• Target: Autophagy,Bcr-Abl,c-Met/HGFR,FGFR,VEGFR,Apoptosis
• Solubility: DMSO:50 mg/mL (77.93 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (3.12 mM)

Bioactivity

• Target IC50:
  c-Met:9 nM
• In Vivo:
  Administration of PHA-665752 induces a dose-dependent tumor growth inhibition of S114 xenografts by 20 %, 39% and 68%, at dose of 7.5, 15, and 30 mg/kg/day, respectively. PHA665752 treatment significantly reduces the tumor growth of NCI-H69, NCI-H441 and A549 in mouse xenografts by 99%, 75%, and 59%, respectively. PHA665752 also significantly inhibits angiogenesis by >85%, due to decreasing the production of vascular endothelial growth factor and increasing the production of the angiogenesis inhibitor thrombospondin-1.
• In Vitro:
  PHA-665752 significantly inhibits c-Met kinase activity with Ki of 4 nM, and exhibits >50-fold selectivity for c-Met compared with various tyrosine and serine-threonine kinases. PHA-665752 potently inhibits the HGF-stimulated c-Met autophosphorylation with IC50 of 25-50 nM. PHA-665752 also significantly blocks HGF- and c-Met-dependent functions such as cell motility and cell proliferation with IC50 of 40-50 nM and 18-42 nM, respectively. In addition, PHA-665752 potently inhibits HGF-stimulated or constitutive phosphorylation of mediators of downstream of c-Met such as Gab-1, ERK, Akt, STAT3, PLC-γ, and FAK in multiple tumor cell lines. PHA-665752 inhibits cell growth in TPR-MET-transformed BaF3 cells with IC50 of <60 nM, and inhibits constitutive cell motility and migration by 92.5% at 0.2 μM. Inhibition of c-Met by PHA665752 (0.2 μM) also induces cell apoptosis of 33.1% and G1 cell cycle arrest with cells in G1 phase increasing from 42.4% to 77.0%. PHA665752 can cooperate with rapamycin to inhibit cell growth of TPR-MET-transformed BaF3 cells and non-small cell lung cancer H441 cells.
• Cell Research:
  For proliferation assays, cells are grown in medium with 0.1% FBS for 48 hours after which they are treated with various concentrations of PHA-665752 in HGF (50 ng/mL) in a medium containing 2% FBS. After 18 hours, cells are incubated with BrdUrd for 1 hour, fixed, and stained with anti-BrdUrd peroxidase-conjugated antibody, and plates are read at 630 nm. For apoptosis assays, cells are grown in medium with 2% FBS in presence and absence of HGF (50 ng/mL) and various concentrations of PHA-665752 for 72 hours. After 72 hours, a mixture containing ethidium bromide and acridine orange is added, and apoptotic cells (bright orange cells or cell fragments) are counted by fluorescence microscopy.(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Flk1, FGFR1, HGFR, Inhibitor, inhibit, cMet, c-Met, cMet/HGFR, c-Met/HGFR, c-Abl, BcrAbl, Autophagy, Apoptosis, PHA 665752, PHA665752, PHA-665752, RON

Compound Identifiers

PubChem CID

10461815