PDGFRβ-IN-1
PDGFRβ-IN-1 is an orally active PDGFRβ inhibitor with an IC50 of 3.9 nM against human PDGFRβ. PDGFRβ-IN-1 selectively inhibits PDGFRβ, blocks its downstream signaling pathways, and promotes its degradation via a non-classical pathway. PDGFRβ-IN-1 inhibits cancer cell proliferation, migration and colony formation, and induces cancer cell apoptosis. PDGFRβ-IN-1 suppresses tumor growth in xenograft models. PDGFRβ-IN-1 can be used for the research of hepatocellular carcinoma.
For research use only. We do not sell to patients.
- Formula: C25H27F2N7O
- Molecular Weight:479.52
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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PDGFRβ 3.9 nM (IC50) |
PDGFRβ-IN-1 (compound A42) potently and selectively inhibits purified PDGFRβ protein with an IC50 of 3.9 nM, and shows 8.3-fold selectivity over PDGFRα. It exhibits moderate selectivity in a panel of 97 kinases, with high selectivity for c-KIT, SRC and AURKA, and narrow selectivity for JAK2, NUAK1 and AURKB[1].
PDGFRβ-IN-1 inhibits the proliferation of human hepatocellular carcinoma cell lines Huh-7 and Hep3B, with IC50 values of 0.39 μM and 0.75 μM, respectively; meanwhile, it exhibits low toxicity to normal human hepatocyte MIHA, with an IC50 of 10.65 μM[1].
PDGFRβ-IN-1 (0.1-0.4 μM; 48 h) inhibits long-term clonogenic growth of Huh-7 and Hep3B human hepatocellular carcinoma cells in a concentration-dependent manner, reduces DNA replication, induces apoptosis, inhibits adhesion to extracellular matrix components, and suppresses migration[1].
PDGFRβ-IN-1 (0.4 μM; 6 h, 0-48 h) inhibits PDGFRβ-mediated signaling pathways in human hepatocellular carcinoma cell lines Huh-7 and Hep3B by suppressing receptor phosphorylation and promoting PDGFRβ degradation via a non-canonical pathway[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Huh-7 and Hep3B human hepatocellular carcinoma cells
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Concentration:0.1, 0.2, 0.4 μM
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Incubation Time:48 h
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Result:Significantly decreased the number of migrated cells in both cell lines in a dose-dependent manner.
Suppressed invasive capacity of Huh-7 cells in a dose-dependent manner.
Showed inhibition substantially greater than that induced by 0.4 μM Sorafenib (HY-10201).
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Cell Line:Huh-7 and Hep3B human hepatocellular carcinoma cells
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Concentration:0.1, 0.2, 0.4 μM
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Incubation Time:48 h
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Result:Effectively suppressed cell migration.
Resulted in only ~30% of the wound area being covered after 48 h when used at 0.4 μM.
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Cell Line:Huh-7 and Hep3B human hepatocellular carcinoma cells
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Concentration:0.1, 0.2, 0.4 μM
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Incubation Time:48 h
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Result:Effectively suppressed cell apoptosis.
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Cell Line:Huh-7 and Hep3B human hepatocellular carcinoma cells
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Concentration:0.4 μM (treatment for signaling pathway analysis)
100 nM (proteasome inhibitor in combination)
20 μM (lysosomotropic agent in combination)
50 μg/mL (protein synthesis inhibitor in combination) -
Incubation Time:6 h (treatment with proteasome inhibitor or lysosomotropic agent in combination)
0, 1, 2, 4, 8, 12, 24, 48 h (treatment with protein synthesis inhibitor in combination) -
Result:Markedly reduced phosphorylation levels of PDGFRβ, STAT3, AKT, and ERK, with stronger inhibition than Sorafenib.
Decreased total PDGFRβ protein levels.
Showed cotreatment with proteasome inhibitor or lysosomotropic agent did not restore PDGFRβ levels.
Shortened PDGFRβ half-life in protein synthesis inhibitor chase experiments, indicating degradation via a noncanonical pathway independent of proteasomes and autophagy-lysosomes.
PDGFRβ-IN-1 (50-200 mg/kg; p.o.; single dose) exhibits a favorable in vivo safety profile in ICR mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude (6-week-old)[1]
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Dosage:15 mg/kg; 30 mg/kg
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Administration:i.p.; daily; 14 days
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Result:Achieved a tumor growth inhibition (TGI) of 45% at 30 mg/kg dose.
Suppressed phosphorylation of PDGFRβ and its downstream effectors STAT3, AKT, and ERK in tumor tissues.
Increased tumor necrosis via H&E staining.
Substantially reduced proliferating cells compared to controls via Ki67 immunostaining.
Maintained stable body weights across treatment groups.
Chemical Information
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Molecular Weight 479.52
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Formula C25H27F2N7O
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SMILES
FC1=CN=C(N=C1NC2=CC=CC3=C2C=CN3CCO)NC4=CC=C(C(F)=C4)N5CCN(CC5)C
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PDGFRβ-IN-1 Related Classifications
HY-187366 Related Classifications
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