PHA-665752
Based on 14 publication(s) in Google Scholar
PHA-665752 is a selective, ATP-competitive, and active-site inhibitor of the catalytic activity of c-Met kinase (Ki=4 nM; IC50=9 nM). PHA-665752 exhibits >50-fold selectivity for c-Met compared with a panel of diverse tyrosine and serine-threonine kinases. PHA-665752 induces apoptosis and cell cycle arrest, and exhibits cytoreductive antitumor activity.
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- Pureza: 98.74%
- No. CAS: 477575-56-7
- Fòrmula: C32H34Cl2N4O4S
- Peso molecular:641.61
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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Actividad biológica
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Chemical Information
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Publications Citing Use of MedChemExpress (MCE) PHA-665752
More- Cancer Res. 2025 Sep 18. [Abstract]
- J Exp Clin Cancer Res. 2024 Nov 20;43(1):308. [Abstract]
- Cancer Lett. 2020 Dec 28;495:41-52. [Abstract]
- Adv Healthc Mater. 2024 Nov 25:e2402884. [Abstract]
- Cell Death Dis. 2022 Apr 21;13(4):387. [Abstract]
- Mol Cancer Ther. 2018 Mar;17(3):603-613. [Abstract]
- Respir Res. 2020 Aug 14;21(1):215. [Abstract]
- Eur J Pharmacol. 2026 Apr 10:1020:178775. [Abstract]
- Int J Cancer. 2019 Aug 1;145(3):748-762. [Abstract]
- Med Oncol. 2020 Mar 12;37(4):24. [Abstract]
- FEBS Open Bio. 2021 Nov;11(11):3115-3125. [Abstract]
- Biomed Res Int. 2020 Mar 14;2020:3635787. [Abstract]
- Am J Transl Res. 2023 Feb 15;15(2):896-913. [Abstract]
- Oncotarget. 2017 Jun 13;8(24):38717-38730. [Abstract]
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Actividad biológica
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A549 | IC50 |
9 nM
Compound: 3, PHA-665752
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Inhibition of human recombinant c-MET kinase expressed in A549 cells assessed as inhibition of HGF-induced autophosphorylation by ELISA method
Inhibition of human recombinant c-MET kinase expressed in A549 cells assessed as inhibition of HGF-induced autophosphorylation by ELISA method
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[PMID: 21812414] |
| HCC827 | IC50 |
15.7 μM
Compound: PHA-665752
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Cytotoxicity against erlotinib-sensitive human HCC827A cells assessed as reduction in cell viability after 72 hrs by MTT assay
Cytotoxicity against erlotinib-sensitive human HCC827A cells assessed as reduction in cell viability after 72 hrs by MTT assay
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[PMID: 27563407] |
| HCC827 | IC50 |
8.9 μM
Compound: PHA-665752
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Cytotoxicity against erlotinib-resistant human HCC827B cells expressing MET assessed as reduction in cell viability after 72 hrs by MTT assay
Cytotoxicity against erlotinib-resistant human HCC827B cells expressing MET assessed as reduction in cell viability after 72 hrs by MTT assay
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[PMID: 27563407] |
| Sf9 | IC50 |
38 nM
Compound: 2, PHA-665752
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Inhibition of GST-tagged c-Met expressed in Sf9 cells
Inhibition of GST-tagged c-Met expressed in Sf9 cells
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[PMID: 19854051] |
| Sf9 | IC50 |
863 nM
Compound: 2, PHA-665752
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Inhibition of GST-tagged VEGFR expressed in Sf9 cells
Inhibition of GST-tagged VEGFR expressed in Sf9 cells
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[PMID: 19854051] |
| TAMH | IC50 |
8.9 μM
Compound: PHA-665752
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Cytotoxicity against TAMH assessed as reduction in cell viability after 24 hrs by cell titer glo based luminescence assay
Cytotoxicity against TAMH assessed as reduction in cell viability after 24 hrs by cell titer glo based luminescence assay
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[PMID: 27563407] |
PHA-665752 is a potent and ATP-competitive inhibitor of c-Met kinase activity with a Ki of 4 nM and an IC50 of 9 nM[1].
PHA-665752 exhibits >50-fold selectivity for c-Met enzyme compared with the majority of kinases evaluated[1].
PHA-665752 shows potent inhibition of c-Met RTK autophosphorylation in NIH3T3 cells engineered to express high levels of c-Met and hepatocyte growth factor (HGF)[1].
PHA-665752 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 (0-1.25 μM; 18 hours) potently inhibits HGF and c-Met-driven phenotypes such as cell growth (proliferation and survival), cell motility, invasion, and/or morphology of a variety of tumor cells[1].
PHA-665752 (0-1.25 μM; 72 hours) induces apoptosis in both the presence and absence of HGF at concentrations that inhibited tyrosine phosphorylation of c-Met in GTL-16 cells[1].
PHA-665752 (0.0125-0.2 μM; 4 hours) potent inhibits HGF-induced c-Met phosphorylation in A549 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:S114 cells, GTL-16 cells, NCI-H441 cells, or BxPC-3 cells
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Concentration:0 μM, 0.002 μM, 0.01 μM, 0.05 μM, 0.25 μM, 1.25 μM
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Incubation Time:18 hours
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Result:Potently inhibited HGF and c-Met-driven cell growth.
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Cell Line:GTL-16 cells
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Concentration:0 μM, 0.002 μM, 0.01 μM, 0.05 μM, 0.25 μM, 1.25 μM
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Incubation Time:72 hours
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Result:Induced apoptosis in both the presence and absence of HGF at concentrations that inhibited tyrosine phosphorylation of c-Met in GTL-16 cells. Immunoblot Analysis.
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Cell Line:A549 cells
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Concentration:0.0125 μM, 0.025 μM,0.05 μM,0.1 μM,0.2 μM
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Incubation Time:4 hours
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Result:Potent inhibited HGF-induced c-Met phosphorylation in A549 cells.
PHA-665752 shows a potent cytoreductive activity in a gastric carcinoma xenograft model[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female athymic mice (nu/nu, 8–12 weeks) bearing S114 or GTL-16 tumor xenografts[1]
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Dosage:7.5 mg/kg/day, 15 mg/kg/day, 30 mg/kg/day
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Administration:Intravenous injection; for 9 days
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Result:Demonstrated statistically significant dose-dependent tumor growth inhibition.
Chemical Information
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No. CAS 477575-56-7
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Appearance Solid
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Peso molecular 641.61
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Fòrmula C32H34Cl2N4O4S
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Color Yellow to orange
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SMILES
O=C(C1=C(NC(/C=C2C(NC3=C\2C=C(C=C3)S(=O)(CC4=C(C=CC=C4Cl)Cl)=O)=O)=C1C)C)N5[C@H](CCC5)CN6CCCC6
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (14)
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Journal Impact Factor
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Most Recent
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Cancer Res
The Prolyl Isomerase PIN1 Impacts Fibroblast Differentiation States and Crosstalk in Pancreatic Cancer. [Abstract]2025 Sep 18. PMID: 40966318 -
J Exp Clin Cancer Res
Dual inhibition of HERs and PD-1 counteract resistance in KRASG12C-mutant head and neck cancer. [Abstract]2024 Nov 20;43(1):308. PMID: 39567998 -
Cancer Lett
Loss of histone lysine methyltransferase EZH2 confers resistance to tyrosine kinase inhibitors in non-small cell lung cancer. [Abstract]2020 Dec 28;495:41-52. PMID: 32920200 -
Adv Healthc Mater
Antitumor Activity of a Bispecific Chimera Targeting EGFR and Met in Gefitinib-Resistant Non-Small Cell Lung Cancer. [Abstract]2024 Nov 25:e2402884. PMID: 39586988 -
Cell Death Dis
HGF/c-Met pathway facilitates the perineural invasion of pancreatic cancer by activating the mTOR/NGF axis. [Abstract]2022 Apr 21;13(4):387. PMID: 35449152 -
Mol Cancer Ther
Afatinib Is a New Therapeutic Approach in Chordoma with a Unique Ability to Target EGFR and Brachyury. [Abstract]2018 Mar;17(3):603-613. PMID: 29237806 -
Respir Res
HGF alleviates septic endothelial injury by inhibiting pyroptosis via the mTOR signalling pathway. [Abstract]2020 Aug 14;21(1):215. PMID: 32795289
PHA-665752 purchased from MedChemExpress. Usage Cited in: Respir Res. 2020 Aug 14;21(1):215. [Abstract]
Immunoblotting reveals that c-Met in the plasma membrane is phosphorylated in response to the binding of HGF, and this c-Met phosphorylation is abolished by PHA-665752 in the LPS-transfected endothelial cells.
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Eur J Pharmacol
Integrative Mendelian randomization and experimental validation unveil novel druggable targets in primary biliary cholangitis. [Abstract]2026 Apr 10:1020:178775. PMID: 41819524 -
Int J Cancer
MET activation confers resistance to cetuximab, and prevents HER2 and HER3 upregulation in head and neck cancer. [Abstract]2019 Aug 1;145(3):748-762. PMID: 30694565 -
Med Oncol
Activation of the HGF/c-MET axis promotes lenvatinib resistance in hepatocellular carcinoma cells with high c-MET expression. [Abstract]2020 Mar 12;37(4):24. PMID: 32166604 -
FEBS Open Bio
CXCR4 promotes gefitinib resistance of Huh7 cells by activating the c-Met signaling pathway. [Abstract]2021 Nov;11(11):3115-3125. PMID: 34555268 -
Biomed Res Int
Upregulation of PDGF Mediates Robust Liver Regeneration after Nanosecond Pulsed Electric Field Ablation by Promoting the HGF/c-Met Pathway. [Abstract]2020 Mar 14;2020:3635787. PMID: 32258116 -
Am J Transl Res
2023 Feb 15;15(2):896-913. PMID: 36915773
PHA-665752 purchased from MedChemExpress. Usage Cited in: Am J Transl Res. 2023 Feb 15;15(2):896-913. [Abstract]
PHA-665752 significantly decreases the migration rate at 24 h and 48 h in Huh-7R cells.
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Oncotarget
Contributions of MET activation to BCR-ABL1 tyrosine kinase inhibitor resistance in chronic myeloid leukemia cells. [Abstract]2017 Jun 13;8(24):38717-38730. PMID: 28418880
PHA-665752 purchased from MedChemExpress. Usage Cited in: Oncotarget. 2017 Jun 13;8(24):38717-38730. [Abstract]
KU812/IR cells are exposed to the indicated concentrations of Imatinib or PHA665752. After incubation for 48 h, the cytoplasmic fractions are extracted and then subjected to SDS-PAGE/immunoblotting with anti-phospho-MET, anti-phospho-ABL1, anti-phospho-ERK1/2, anti-phospho-AKT, anti-phospho-JNK, anti-MET, anti-ABL1, anti-ERK1/2, anti-AKT, and anti-JNK antibodies. Anti-β-ACTIN antibody is used as internal standards.
Solvente y solubilidad
DMSO : 25 mg/mL (38.96 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (3.90 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (3.90 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureza y Documentación
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Ficha de datos (281 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Christensen JG, et al. A selective small molecule inhibitor of c-Met kinase inhibits c-Met-dependent phenotypes in vitro and exhibits cytoreductive antitumor activity in vivo. Cancer Res. 2003 Nov 1;63(21):7345-55. [Content Brief]
[2]. Ma PC. et al. A selective small molecule c-MET Inhibitor, PHA665752, cooperates with rapamycin. Clin Cancer Res. 2005 Mar 15;11(6):2312-9. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.5586 mL | 7.7929 mL | 15.5858 mL | 38.9645 mL |
| 5 mM | 0.3117 mL | 1.5586 mL | 3.1172 mL | 7.7929 mL | |
| 10 mM | 0.1559 mL | 0.7793 mL | 1.5586 mL | 3.8964 mL | |
| 15 mM | 0.1039 mL | 0.5195 mL | 1.0391 mL | 2.5976 mL | |
| 20 mM | 0.0779 mL | 0.3896 mL | 0.7793 mL | 1.9482 mL | |
| 25 mM | 0.0623 mL | 0.3117 mL | 0.6234 mL | 1.5586 mL | |
| 30 mM | 0.0520 mL | 0.2598 mL | 0.5195 mL | 1.2988 mL |
PHA-665752 Related Classifications
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