Zamaporvint

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Zamaporvint (RXC004) 是一种具有口服活性的选择性 Wnt 抑制剂。Zamaporvint 靶向膜结合邻酰基转移酶 Porcupine 并抑制 Wnt 配体棕榈酰化、分泌和通路激活。Zamaporvint 显示出良好的药代动力学特征，并在依赖 Wnt 配体的结直肠和胰腺细胞系中显示出强效的抗增殖作用。Zamaporvint 具有多种抗肿瘤机制，可用于癌症研究。

Zamaporvint (RXC004) is an orally active and selective inhibitor of Wnt. Zamaporvint targete membrane-bound o-acyltransferase Porcupine and inhibited Wnt ligand palmitoylation, secretion, and pathway activation. Zamaporvint displays a favorable pharmacokinetic profile and shows potent antiproliferative effects in Wnt ligand-dependent colorectal and pancreatic cell lines. Zamaporvint possesses multiple antitumor mechanisms and can be used in cancer research.

Western Blot Analysis Cell Line:L-Wnt5a Concentration:300 nM Incubation Time:48 h Result:Activated the β-catenin-responsive luciferase reporter gene in a concentration-dependent manner, with an IC50 of 64 pmol/L.Apoptosis Analysis Cell Line: L-Wnt5a Concentration:100 nM Incubation Time:24 h Result:Downregulated c-Myc mRNA and reduce the proportion of cells in S-phase, and strongly inhibited expression of the mitosis marker phospho-histone-H3 in cells with upstream aberrations in Wnt pathway components.

Animal Model:SCID-Beige mice were dosed at Translational Drug Discovery with vehicleDosage:1.5 mg/kg or 5 mg/kg; 5 mg/kgAdministration:1.5 mg/kg or 5 mg/kg orally twice daily, or 5 mg/kg RXC004 orally once daily, for 28 daysResult:Reduced in tumor growth, and inhibition of Wnt-responsive gene expression including cMyc, was observed in the Wnt ligand–dependent SNU-1411, AsPC1, and HPAFII models.No effected tumor growth in the Wnt ligand–independent HCT116 xenograft mode.Animal Model:HPAF-II (5 × 106 cells; athymic nude mice), AsPC1 (3 × 106 cells; athymic nude mice), and SNU-1411 (1×107 cells; NOD-SCID mice) were implanted bilaterally, subcutaneously, whereas HCT116 (3 × 106 cells; athymic nude mice) were implanted in a single flank Dosage:Dosing was either 1.5 mg/kg twice daily RXC004 for 7–13 days then once daily for the remainder of study (up to 29 days), or 28 days 1.5 mg/kg twice daily RXC004 for HCT116 Administration:p.o.Result:Demonstrated to inhibit tumor growth and Wnt-responsive gene expressionAnimal Model:B16F10/C57BL/6 syngeneic model was performed at Axis Bioservices. Mouse B16F10 cells (2 × 105) were subcutaneously implanted in flanks of the immunocompetent male C57BL/6 miceDosage:5 mg/kg once daily Administration: p.o.Result: Inhibited tumor growth and improved model survival.Animal Model:CT26/BALB/c syngeneic model was performed at ProQuinase GmbH. Mouse CT26 cells (5 × 105) were subcutaneously implanted in the flanks of the immunocompetent female BALB/c mice Dosage:1.5 or 5 mg/kg (once daily).Administration:p.o.Result:Increased CD8+/regulatory T cell ratio.

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1900754-56-4

439.39

C21H16F3N7O

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 125 mg/mL (284.49 mM; 超声助溶 )

O=C(NC1=NC=C(C=C1)C=2N=CC=NC2)CN3C=NC(C=4C=CN=C(C4)C(F)(F)F)=C3C

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(-20℃)

With Ice Pack

≥ 2 years