VEGFR2-IN-84
VEGFR2-IN-84 is an orally active, multi-targeted tyrosine kinase inhibitor based on a naphthalene ring scaffold. VEGFR2-IN-84 inhibits VEGFR2 with sub-nanomolar affinity and broadly targets kinases including Kit, FGFR, PDGFR, and Ret. By competitively binding to the ATP-binding pocket, VEGFR2-IN-84 blocks the phosphorylation of VEGFR2 and its downstream AKT/ERK signaling pathway, thereby significantly inhibiting endothelial cell proliferation, migration, and tumor angiogenesis. VEGFR2-IN-84 exhibits broad-spectrum antiproliferative activity against various solid tumors such as liver cancer, lung cancer, and renal cancer, shows weak toxicity to normal cells, and has superior potency to Lenvatinib (HY-10981). VEGFR2-IN-84 possesses favorable pharmacokinetic properties and high safety (LD50>2000 mg/kg), and can be used in related studies of various malignant tumors.
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- CAS No.: 861877-12-5
- 화학식: C25H18N4O4S
- 분자량:470.50
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- 순도&문서
- References
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Help & FAQs
All VEGFR Isoforms
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Biological Activity
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VEGFR2 0.303 nM (EC50) |
PDGFRα 0.742 nM (EC50) |
PDGFRβ 2.12 nM (EC50) |
Flt-4 1.35 nM (EC50) |
FGFR1 195 nM (EC50) |
FGFR2 4.43 nM (EC50) |
FGFR3 28.7 nM (EC50) |
Flt-1 1.61 nM (EC50) |
VEGFR2-IN-84 (E20) (4.92 nM; 96 h) significantly inhibits VEGF-induced proliferation of HUVEC cells, with approximately 10-fold the activity of Lenvatinib (HY-10981)[1].
VEGFR2-IN-84 (10-1000 nM; 48 h) dose-dependently inhibits the phosphorylation of VEGFR2 and its downstream molecules AKT and ERK in HUVEC, A549 and HepG2 cells, and exhibits superior activity to Lenvatinib[1].
VEGFR2-IN-84 (8.53-14.1 μM; 72 h) exhibits weak inhibitory activity against normal cells LO2, HEK293T and BEAS-2B, showing favorable tumor cell selectivity[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Human umbilical vein endothelial cells (HUVECs)
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Concentration:IC50
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Incubation Time:96 h
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Result:Significantly inhibited hVEGF-165 (20 ng/mL)-induced proliferation of HUVECs with an IC50 value of 4.92 nM, which was over 10-fold more potent than lenvatinib (IC50=51.2 nM).
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Cell Line:HUVECs, A549 cells, HepG2 cells
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Concentration:10 nM, 1000 nM
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Incubation Time:48 h
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Result:Dose-dependently suppressed hVEGF-165 (50 ng/mL)-induced phosphorylation of VEGFR2 (Tyr1175), AKT (Ser473), and ERK1/2 (Thr202/Tyr204) in HUVECs.
Significantly reduced p-VEGFR2 and p-ERK levels.
Dose-dependently inhibited the phosphorylation of VEGFR2, AKT, and ERK in A549 and HepG2 cells, and exhibited more potent inhibitory effects than lenvatinib at the same concentrations.
VEGFR2-IN-84 (30-60 mg/kg; p.o.; once daily; 20-30 days) dose-dependently inhibits tumor growth in male BALB/c nude mouse xenograft models of A549 lung cancer, 786-O renal cell carcinoma, and 8305C thyroid carcinoma, respectively, and exhibits superior efficacy over Lenvatinib at the same dose[1].
VEGFR2-IN-84 (2 mg/kg; tail vein injection; single dose; 24 h) exhibits a moderate elimination half-life (T1/2=5.05 h) and plasma exposure (AUC0-∞=1970 ng?h/mL) in healthy 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:Male BALB/c nude mice (4-5 weeks old, 15-17 g), HepG2 hepatocellular carcinoma subcutaneous xenograft model[1]
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Dosage:50 mg/kg
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Administration:Intragastric (p.o.) administration, once daily (qd)
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Result:Significantly inhibited the growth of HepG2 xenografts with a tumor growth inhibition (TGI) rate of 94.3%, which was superior to lenvatinib (TGI=83.6%) at the same dose.
No significant body weight loss or overt signs of toxicity were observed throughout the experimental period.
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Animal Model:Male BALB/c nude mice (4-5 weeks old, 15-17 g), A549 non-small cell lung cancer subcutaneous xenograft model[1]
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Dosage:30 mg/kg or 60 mg/kg
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Administration:Intragastric (p.o.) administration, once daily (qd)
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Result:Exhibited dose-dependent antitumor activity.
At 30 mg/kg, the TGI rate was 76.9%, which was superior to lenvatinib (TGI=61.3%) at the same dose.
At 60 mg/kg, achieved a TGI rate of 95.7%, significantly outperforming lenvatinib (TGI=84.6%).
No significant body weight loss was observed.
Chemical Information
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CAS No. 861877-12-5
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분자량 470.50
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화학식 C25H18N4O4S
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SMILES
NC(C1=C(C=C(C2=C1)N=CC=C2OC3=CC4=C(C=C3)C(C(NC5=NC=CS5)=O)=CC=C4)OC)=O
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
VEGFR2-IN-84 Related Classifications
HY-182354 Related Classifications
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