Vatalanib free base

• CAT Number: I002634
• CAS Number: 212141-54-3
• Molecular Formula: C₂₀H₁₅ClN₄
• Molecular Weight: 346.81
• Purity: ≥95%
• Synonyms: N-(4-chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine
• Target: VEGFR
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IC50: 37 nM (VEGFR2/KDR) [1]
• InChI: InChI=1S/C20H15ClN4/c21-15-5-7-16(8-6-15)23-20-18-4-2-1-3-17(18)19(24-25-20)13-14-9-11-22-12-10-14/h1-12H,13H2,(H,23,25)
• InChIKey: YCOYDOIWSSHVCK-UHFFFAOYSA-N
• SMILES: C1=CC=C2C(=C1)C(=NN=C2NC3=CC=C(C=C3)Cl)CC4=CC=NC=C4

Vatalanib free base (PTK787 free base) is an inhibitor of VEGFR2/KDR with IC50 of 37 nM, less potent against VEGFR1/Flt-1, 18-fold against VEGFR3/Flt-4.IC50 value: 37 nM (VEGFR2/KDR) [1]Target: VEGFR2in vitro: Vatalanib also inhibits Flk, c-Kit and PDGFRβ with IC50 of 270 nM, 730 nM and 580 nM, respectively. Furthermore, Vatalanib shows the anti-proliferation effect by inhibiting thymidine incorporation induced by VEGF in HUVECs with and IC50 of 7.1 nM, and dose-dependently suppresses VEGF-induced survival and migration of endothelial cells in the same dose range without cytotoxic or antiproliferative effect on cells that do not express VEGF receptors [1]. A recent study shows that Vatalanib significantly inhibits the growth of hepatocellular carcinoma cells and enhances the IFN/5-FU induced apoptosis by increasing proteins levels of Bax and reduced Bcl-xL and Bcl-2 [2].in vivo: Vatalanib induces dose-dependent inhibition of the angiogenic response to VEGF and PDGF in both a growth factor implant model and a tumor cell-driven angiogenesis model after once-daily oral dosing (25-100 mg/kg). In the same dose range, Vatalanib also inhibits the growth and metastasesof several human carcinomas in nude mice without significant effect on circulating blood cells or bone marrow leukocytes [1].

Reference

[1]. Wood JM, et al. PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res. 2000, 60(8), 2178-2189.

[2]. Murakami M, et al. Tyrosine kinase inhibitor PTK/ZK enhances the antitumor effects of interferon-α/5-fluorouracil therapy for hepatocellular carcinoma cells. Ann Surg Oncol. 2011, 18(2), 589-596.