| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
|
Purity: ≥98%
PHA-665752 (PHA665752) is a novel, potent, selective and ATP-competitive small molecule inhibitor of c-Met Kinase with potential antitumor activity. In cell-free experiments, it inhibits c-Met with an IC50 of 9 nM and demonstrates >50-fold selectivity in inhibiting c-Met relative to other kinases like RTKs or STKs. It has the ability to target human cancers with overactivated c-Met. By inhibiting the hepatocyte growth factor-induced cell proliferation and radioresistance in nasopharyngeal carcinoma cells, it demonstrates strong anti-proliferative activity in vitro.
| Targets |
c-Met (IC50 = 9 nM); RON (IC50 = 68 nM); Flk1 (IC50 = 200 nM)
|
|
|---|---|---|
| ln Vitro |
|
|
| ln Vivo |
|
|
| Enzyme Assay |
The c-Met assay uses the GST-fusion protein containing the c-Met kinase domain. Based on the phosphorylation of kinase peptide substrates or poly-glu-tyr in the presence of ATP and divalent cations (MgCl2 or MnCl2 10–20 mM), PHA-665752's IC50 value for the inhibition of c-Met is determined. For c-Met, the linear range—that is, the duration during which the rate stays equal to the initial rate—is established, and the kinetic measurement and IC50 calculation are carried out inside of this range.
|
|
| Cell Assay |
Cells are grown in 0.1% FBS medium for 48 hours in order to perform proliferation assays. Afterward, the cells are treated with varying concentrations of PHA-665752 in HGF (50 ng/mL) in a medium containing 2% FBS. Following 18 hours, cells are fixed, stained with an anti-BrdUrd peroxidase-conjugated antibody, and then incubated with BrdUrd for an hour. The plates are then read at 630 nm. Cells are grown in 2% FBS medium with and without HGF (50 ng/mL) and different concentrations of PHA-665752 for 72 hours in order to perform apoptosis assays. After 72 hours, a mixture containing acridine orange and ethidium bromide is added, and fluorescent microscopy is used to count the number of apoptotic cells (bright orange cells or cell fragments).
|
|
| Animal Protocol |
Female athymic mice (nu/nu) bearing S114 or GTL-16 tumor xenografts
~30 mg/kg/day Injection via bolus i.v. |
|
| References |
| Molecular Formula |
C32H34CL2N4O4S
|
|
|---|---|---|
| Molecular Weight |
641.61
|
|
| Exact Mass |
640.17
|
|
| Elemental Analysis |
C, 59.90; H, 5.34; Cl, 11.05; N, 8.73; O, 9.97; S, 5.00
|
|
| CAS # |
477575-56-7
|
|
| Related CAS # |
|
|
| Appearance |
Solid powder
|
|
| SMILES |
CC1=C(NC(=C1C(=O)N2CCC[C@@H]2CN3CCCC3)C)/C=C\4/C5=C(C=CC(=C5)S(=O)(=O)CC6=C(C=CC=C6Cl)Cl)NC4=O
|
|
| InChi Key |
OYONTEXKYJZFHA-SSHUPFPWSA-N
|
|
| InChi Code |
InChI=1S/C32H34Cl2N4O4S/c1-19-29(35-20(2)30(19)32(40)38-14-6-7-21(38)17-37-12-3-4-13-37)16-24-23-15-22(10-11-28(23)36-31(24)39)43(41,42)18-25-26(33)8-5-9-27(25)34/h5,8-11,15-16,21,35H,3-4,6-7,12-14,17-18H2,1-2H3,(H,36,39)/b24-16-/t21-/m1/s1
|
|
| Chemical Name |
(3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one
|
|
| Synonyms |
PHA-665752; PHA665752; PHA 665752
|
|
| HS Tariff Code |
2934.99.9001
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
|
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5586 mL | 7.7929 mL | 15.5858 mL | |
| 5 mM | 0.3117 mL | 1.5586 mL | 3.1172 mL | |
| 10 mM | 0.1559 mL | 0.7793 mL | 1.5586 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
|
 |
 |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
