(2R)-1-[[5-[(Z)-[5-[[(2,6-DICHLOROPHENYL)METHYL]SULFONYL]-1,2-DIHYDRO-2-OXO-3H-INDOL-3-YLIDENE]METHYL]-2,4-DIMETHYL-1H-PYRROL-3-YL]CARBONYL]-2-(1-PYRROLIDINYLMETHYL)PYRROLIDINE PHA 665752
(3Z)-5-[(2,6-dichlorobenzyl)sulfonyl]-3-[(3,5-dimethyl-4-{[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl]carbonyl}-1H-pyrrol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one
CAS: 477575-56-7
Molecular Formula: C32H34Cl2N4O4S
(2R)-1-[[5-[(Z)-[5-[[(2,6-DICHLOROPHENYL)METHYL]SULFONYL]-1,2-DIHYDRO-2-OXO-3H-INDOL-3-YLIDENE]METHYL]-2,4-DIMETHYL-1H-PYRROL-3-YL]CARBONYL]-2-(1-PYRROLIDINYLMETHYL)PYRROLIDINE PHA 665752 - Names and Identifiers
(2R)-1-[[5-[(Z)-[5-[[(2,6-DICHLOROPHENYL)METHYL]SULFONYL]-1,2-DIHYDRO-2-OXO-3H-INDOL-3-YLIDENE]METHYL]-2,4-DIMETHYL-1H-PYRROL-3-YL]CARBONYL]-2-(1-PYRROLIDINYLMETHYL)PYRROLIDINE PHA 665752 - Physico-chemical Properties
| Molecular Formula | C32H34Cl2N4O4S |
| Molar Mass | 641.61 |
| Density | 1.404 |
| Boling Point | 890.2±65.0 °C(Predicted) |
| Flash Point | 492.157°C |
| Solubility | DMSO: ≥20mg/mL |
| Vapor Presure | 0mmHg at 25°C |
| Appearance | powder |
| Color | light yellow to light brown |
| pKa | 11.39±0.20(Predicted) |
| Storage Condition | Sealed in dry,2-8°C |
| Refractive Index | 1.656 |
| In vitro study | PHA-665752 significantly inhibited c-Met kinase activity with a Ki of 4 nM and an IC50 of 9 nM and a 50-fold higher selectivity for c-Met compared to various tyrosine and serine-threonine kinases. PHA-665752 effective inhibition of HGF stimulated c-Met autophosphorylation, IC50 25-50 nM. PHA-665752 also significantly inhibited HGF-and c-Met-dependent functions such as cell motility and cell proliferation with an IC50 of 40-50 nM and 18-42 nM, respectively. In addition, PHA-665752 acts on a variety of tumor cell lines, effectively inhibiting phosphorylation of HGF-stimulated or constitutive c-Met of downstream regulators such as Gab-1, ERK, Akt, STAT3, PLC-γ, and FAK. PHA-665752 inhibited cell growth in TPR-MET-transformed BaF3 cells in a dose-dependent manner, and 0.2 μm PHA-665752 also inhibited constitutive cell viability and migration with an inhibition rate of 92.5%. Inhibition of 0.2 μm PHA665752 by c-Met also induced apoptosis in 33.1% cells and increased G1 phase cells from 42.4% to 77.0%. PHA-665752 significantly inhibited c-Met kinase activity with K 1 at 4 nM and IC50 at 9 nM, and was 50-fold more selective for c-Met than various tyrosine and serine-threonine kinases. PHA-665752 effective inhibition of HGF stimulated c-Met autophosphorylation, IC50 25-50 nM. PHA-665752 also significantly inhibited HGF-and c-Met-dependent functions such as cell motility and cell proliferation with an IC50 of 40-50 nM and 18-42 nM, respectively. In addition, PHA-665752 acts on a variety of tumor cell lines, effectively inhibiting phosphorylation of HGF-stimulated or constitutive c-Met of downstream regulators such as Gab-1, ERK, Akt, STAT3, PLC-γ, and FAK. PHA-665752 inhibited cell growth in TPR-MET-transformed BaF3 cells in a dose-dependent manner, and 0.2 μm PHA-665752 also inhibited constitutive cell viability and migration with an inhibition rate of 92.5%. 0.2 M PHA665752 inhibited c-Met, also induced 33.1% cell apoptosis, and the G1 phase cells from 42.4% Increased to 77.0%. |
| In vivo study | Consistent with c-Met inhibition of phosphorylation and signal transduction in vivo, PHA-665752 treatment of S114 xenografts inhibited tumor growth in a dose-dependent manner, with doses of 7.5, 15, and 30 mg/kg daily, tumor growth inhibition was 20%, 39% and 68%, respectively. Treatment of the mouse xenograft tumor model with PHA665752 significantly reduced tumor growth by 99%,75%, and 59% in NCI-H69, NCI-H441, and A549, respectively. PHA665752 also significantly inhibited angiogenesis by more than 85%, decreased the production of endothelial growth factor, and increased the production of angiogenesis inhibitor platelet -1. consistent with c-Met inhibition of phosphorylation and signal transduction in vivo, PHA-665752 treatment of S114 xenografts inhibited tumor growth in a dose-dependent manner, with 7.5, 15, and 30 mg/kg dose treatment, tumor growth inhibition was 20%, 39% and 68%, respectively. Treatment of the mouse xenograft tumor model with PHA665752 significantly reduced tumor growth by 99%,75%, and 59% in NCI-H69, NCI-H441, and A549, respectively. PHA665752 also significantly inhibited angiogenesis by more than 85%, decreased the production of endothelial growth factor, and increased the production of angiogenesis inhibitor platelet -1. |
(2R)-1-[[5-[(Z)-[5-[[(2,6-DICHLOROPHENYL)METHYL]SULFONYL]-1,2-DIHYDRO-2-OXO-3H-INDOL-3-YLIDENE]METHYL]-2,4-DIMETHYL-1H-PYRROL-3-YL]CARBONYL]-2-(1-PYRROLIDINYLMETHYL)PYRROLIDINE PHA 665752 - Risk and Safety
| WGK Germany | 3 |
(2R)-1-[[5-[(Z)-[5-[[(2,6-DICHLOROPHENYL)METHYL]SULFONYL]-1,2-DIHYDRO-2-OXO-3H-INDOL-3-YLIDENE]METHYL]-2,4-DIMETHYL-1H-PYRROL-3-YL]CARBONYL]-2-(1-PYRROLIDINYLMETHYL)PYRROLIDINE PHA 665752 - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 1.559 ml | 7.793 ml | 15.586 ml |
| 5 mM | 0.312 ml | 1.559 ml | 3.117 ml |
| 10 mM | 0.156 ml | 0.779 ml | 1.559 ml |
| 5 mM | 0.031 ml | 0.156 ml | 0.312 ml |
Last Update：2024-01-02 23:10:35
(2R)-1-[[5-[(Z)-[5-[[(2,6-DICHLOROPHENYL)METHYL]SULFONYL]-1,2-DIHYDRO-2-OXO-3H-INDOL-3-YLIDENE]METHYL]-2,4-DIMETHYL-1H-PYRROL-3-YL]CARBONYL]-2-(1-PYRROLIDINYLMETHYL)PYRROLIDINE PHA 665752 - Reference Information
| biological activity | PHA-665752 is an effective, selective, ATP competitive c-Met inhibitor with IC50 of 9 nM and more than 50 times higher selectivity to c-Met than RTKs and STKs. PHA-665752 is an effective, selective, ATP competitive c-Met inhibitor. in cell-free test, IC50 is 9 nM, and its selectivity for c-Met is more than 50 times higher than that for RTKs and STKs. |
| in vitro study | PHA-665752 significantly inhibit c-Met kinase activity, Ki is 4 nM,IC50 is 9 nM, and compared with various tyrosine and serine-threonine kinases, the selectivity of acting on c-Met is more than 50 times higher. PHA-665752 effectively inhibited c-Met autophosphorylation stimulated by HGF, IC50 was 25-50 nM. PHA-665752 also significantly inhibited HGF-and c-Met-dependent functions, such as cell movement and cell proliferation, with IC50 of 40-50 nM and 18-42 nM respectively. In addition, PHA-665752 acts on a variety of tumor cell lines to effectively inhibit the phosphorylation of HGF-stimulated or constitutive c-Met downstream regulators such as Gab-1, ERK, Akt, STAT3, PLC-γ, and FAK. PHA-665752 acts on TPR-MET-transformed BaF3 cells and inhibits cell growth. This effect is dose-dependent. 0.2 μM PHA-665752 also inhibits the viability and migration of constitutive cells, with an inhibition rate of 92.5%. 0.2 μM PHA665752 inhibit c-Met, induce apoptosis of 33.1% cells, and increase G1 phase cells from 42.4% to 77.0%. PHA-665752 significantly inhibited c-Met kinase activity, K I was 4 nM,IC50 was 9 nM, and compared with various tyrosine and serine-threonine kinases, the c-Met selectivity was more than 50 times higher. PHA-665752 effectively inhibit c-Met autophosphorylation stimulated by HGF, IC50 is 25-50 nM. PHA-665752 also significantly inhibited HGF-and c-Met-dependent functions, such as cell movement and cell proliferation, with IC50 of 40-50 nM and 18-42 nM respectively. In addition, PHA-665752 acts on a variety of tumor cell lines to effectively inhibit the phosphorylation of HGF-stimulated or constitutive c-Met downstream regulators such as Gab-1, ERK, Akt, STAT3, PLC-γ, and FAK. PHA-665752 acts on TPR-MET-transformed BaF3 cells and inhibits cell growth. This effect is dose-dependent. 0.2 μM PHA-665752 also inhibits the viability and migration of constitutive cells, with an inhibition rate of 92.5%. 0.2 μM PHA665752 inhibit c-Met, induce apoptosis of 33.1% cells, and increase G1 phase cells from 42.4% to 77.0%. |
| in vivo research | is consistent with in vivo inhibition of c-Met phosphorylation and signal transduction. S114 transplanted tumor is PHA-665752 treated and tumor growth is inhibited. this effect is dose-dependent. tumor growth inhibition is 20%, 39% and 68% respectively when treated at doses of 7.5, 15 and 30 mg/kg per day. PHA665752 treatment of mouse transplanted tumor model significantly reduced tumor growth, reducing NCI-H69, NCI-H441 and A549 tumor growth by 99%,75% and 59% respectively. PHA665752 also significantly inhibit angiogenesis, inhibit more than 85%, reduce the yield of endothelial growth factor, and increase the yield of angiogenesis inhibitor platelet -1. consistent with the inhibition of c-Met phosphorylation and signal transduction in vivo, S114 transplanted tumor was PHA-665752 treated to inhibit tumor growth. this effect was dose-dependent, with tumor growth inhibition of 20%, 39% and 68% treated at 7.5, 15, and 30 mg/kg doses per day, respectively. PHA665752 treatment of mouse transplanted tumor model significantly reduced tumor growth, reducing NCI-H69, NCI-H441 and A549 tumor growth by 99%,75% and 59% respectively. PHA665752 also significantly inhibit angiogenesis, inhibit more than 85%, reduce the yield of endothelial growth factor, and increase the yield of angiogenesis inhibitor platelet -1. |
| target | TargetValue c-Met 9 nM RON (Cell-Free Assay) 68 nM Flk1 (Cell-Free Assay) 200 nM |
| Target | Value |
| c-Met (Cell-free assay) | 9 nM |
| RON (Cell-free assay) | 68 nM |
| Flk1 (Cell-free assay) | 200 nM |
Last Update：2024-04-09 20:52:54
![(2R)-1-[[5-[(Z)-[5-[[(2,6-DICHLOROPHENYL)METHYL]SULFONYL]-1,2-DIHYDRO-2-OXO-3H-INDOL-3-YLIDENE]METHYL]-2,4-DIMETHYL-1H-PYRROL-3-YL]CARBONYL]-2-(1-PYRROLIDINYLMETHYL)PYRROLIDINE PHA 665752](http://res.chembk.com/assets/images/structure/307467.gif)
Supplier List
Spot supply
Product Name: PHA-665752 Visit Supplier Webpage Request for quotationCAS: 477575-56-7
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
Spot supply
Product Name: PHA-665752 Visit Supplier Webpage Request for quotationCAS: 477575-56-7
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
View History