VEGFR-3-IN-1

• CAT Number: I045382
• CAS Number: 2756668-73-0
• Molecular Formula: C29H29ClF3N7OS
• Molecular Weight: 616.10
• Purity: ≥95%
• Synonyms: N-[4-chloro-3-(trifluoromethyl)phenyl]-4-[6-[4-(4-methylpiperazin-1-yl)phenyl]thieno[2,3-d]pyrimidin-4-yl]piperazine-1-carboxamide
• InChI: InChI=1S/C29H29ClF3N7OS/c1-37-8-10-38(11-9-37)21-5-2-19(3-6-21)25-17-22-26(34-18-35-27(22)42-25)39-12-14-40(15-13-39)28(41)36-20-4-7-24(30)23(16-20)29(31,32)33/h2-7,16-18H,8-15H2,1H3,(H,36,41)
• InChIKey: ZYZUOYYVHYGMDE-UHFFFAOYSA-N
• SMILES: CN1CCN(CC1)C2=CC=C(C=C2)C3=CC4=C(N=CN=C4S3)N5CCN(CC5)C(=O)NC6=CC(=C(C=C6)Cl)C(F)(F)F

VEGFR-3-IN-1 is a potent and selective VEGFR3 inhibitor with an IC50 of 110.4 nM. VEGFR-3-IN-1 significantly inhibits proliferation and migration of VEGF-C-induced human dermal lymphatic endothelial cells (HDLEC), MDA-MB-231, and MDA-MB-436 cells by inactivating the VEGFR3 signaling pathway, and also effectively inhibits breast cancer growth[1].
VEGFR-3-IN-1 (compound 38k) exhibits a significantly higher antiproliferative activity on MDA-MB-231 and MDA-MB-436 cells than 10 (IC50 > 50 μM), with IC50 values of 2.22 and 3.50 μM, respectively[1].
VEGFR-3-IN-1 markedly suppresses the phosphorylation of VEGFR3 and its downstream proteins in a dose-dependent manner[1].
VEGFR-3-IN-1 (50, 25 mg/kg; p.o.) reduces the tumor volume, and displays the strongest inhibitory activity in mice, with a growth inhibition rate of 61.9%[1].
VEGFR-3-IN-1 (10 mg/kg; p.o.) treatment shows the Cmax, AUC0-t , AUC0-∞ and t1/2 values of 420 ng/mL, 9219 ng h/mL, 12304 ng h/mL and 16 hours, respectively[1].

Reference

[1]. Li Y, Yang G, et al. Discovery, Synthesis, and Evaluation of Highly Selective Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) Inhibitor for the Potential Treatment of Metastatic Triple-Negative Breast Cancer. J Med Chem. 2021;64(16):12022-12048.
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