PHA-665752(PHA665752)|Met inhibitor|DC Chemicals

Cas No.:	477575-56-7
Chemical Name:	(R,Z)-5-(2,6-dichlorobenzylsulfonyl)-3-((3,5-dimethyl-4-(2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl)-1H-pyrrol-2-yl)methylene)indolin-2-one
Synonyms:	PHA 665752; PHA665752
SMILES:	O=C(C1=C(NC(/C=C2C(NC3=C2C=C(C=C3)S(=O)(CC4=C(C=CC=C4Cl)Cl)=O)=O)=C1C)C)N5[C@H](CCC5)CN6CCCC6
Formula:	C₃₂H₃₄Cl₂N₄O₄S
M.Wt:	641.61
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	PHA-665752 is a potent, selective and ATP-competitive c-Met inhibitor with IC50 of 9 nM, >50-fold selectivity for c-Met than RTKs or STKs.
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 [1]. 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 [3].
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 [1]. 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 [2].

Cat. No.	Product name	Field of application
DC74383	WM-S1-030	WM-S1-030 is a highly potent, specific inhibitor of recepteur d'origine nantais (RON kinase, MST1R) with IC50 of 0.39 nM in in vitro enzyme activity.
DC74382	Tepotinib	Tepotinib (EMD1214063, MSC2156119) is a potent, specific and ATP-competitive inhibitor of MET (HGFR) with IC50 of 23 nM for MET WT autophosphorylation and 2.2-42.6 nM for M1268T, Y1248H, H1112Y, L1213V, H1112L, V1110I, V1206L, and V1238I MET-mutated varia
DC72770	Zongertinib	Zongertinib is a potent tyrosine kinase inhibitor. Zongertinib can be used as an antineoplastic agent. Zongertinib also has been tested as pHER2 and EGFR inhibitor inhibiting a wide variety of cancers.
DC28722	BAY-474	BAY-474 is a tyrosine-protein kinase c-Met inhibitor. BAY-474 acts as an epigenetics probe.
DC7376	BMS777607	BMS-777607 is a Met-related inhibitor for c-Met, Axl, Ron and Tyro3 with IC50 of 3.9 nM, 1.1 nM, 1.8 nM and 4.3 nM.
DC7294	SGX-523	SGX-523 is a selective Met inhibitor with IC50 of 4 nM, no activity to BRAFV599E, c-Raf, Abl and p38α.
DC7230	PHA-665752	PHA-665752 is a potent, selective and ATP-competitive c-Met inhibitor with IC50 of 9 nM, >50-fold selectivity for c-Met than RTKs or STKs.
DC11543	Glumetinib	Glumetinib (SCC 244) is a novel potent and highly selective inhibitor of c-Met kinase with IC50 of 0.42 nM.
DC7342	Foretinib(XL880)	Foretinib (GSK1363089; XL880; EXEL-2880; GSK089) is an ATP-competitive inhibitor of HGFR and VEGFR, mostly for Met and KDR with IC50 of 0.4 nM and 0.9 nM. Less potent against Ron, Flt-1/3/4, Kit, PDGFRα/β and Tie-2, and little activity to FGFR1 and EGFR.