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Zamaporvint

MCE China：Zamaporvint

Brand：MedChemExpress (MCE)

Cat. No.HY-153855

CAS：1900754-56-4

Synonyms：RXC004

Purity：99.76%

Storage：Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month

Shipping：Room temperature in continental US; may vary elsewhere.

Description：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.

In Vitro：Zamaporvint (300 nM, 48 h) treatment of L- wnt3a cells reduce the ability of conditioned medium to activate the β-catenin-responsive luciferase reporter gene in a concentration-dependent manner, with an IC50 of 64 pM, and the addition of recombinant Wnt3a restore the luciferase activity, suggesting no effect on downstream Wnt signaling[1]. The effect of Zamaporvint (100 nM, 24 hr) on proliferation reflects a concentration-dependent downregulation of c-Myc mRNA. Reduced the proportion of cells in S phase and strongly suppressed the expression of the mitotic marker phospho-histone-H3 in cells with abnormal upstream components of the Wnt pathway, indicative of cell cycle arrest, and was found to have reduced immunosuppression at the same dose as after administration Sexual support[1] . Zamaporvint (20 μM, 18 h) in plasma across species ranged from 2.5% to 7.5%, microsomal CLint values ranged from 3.9 to 31.6 μL/min?mg, with mouse having the lowest and dog the highest predicted clearances, rodents and humans display low clearance[1]. Zamaporvint (10 μM, 2 h) has good intrinsic permeability, showing some evidence of efflux in MDR1-MDCKII cells but not in Caco-2 cells[1].

In Vivo：Zamaporvint (1.5 mg/kg or 5 mg/kg orally twice daily, or 5 mg/kg Zamaporvint orally once daily, for 28 days) reduces 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, and no effected tumor growth in the Wnt ligand–independent HCT116 xenograft mode[1]. Zamaporvint (1.5 mg/kg, 5 mg/kg, once daily) reduces Ki67-positive cells in the total tumor area, and its effect is more pronounced in differentiated tumor areas, and by inhibiting immune evasion in the B16F10 "cold" tumor model Antitumor effect [1]. Zamaporvint (1.5 or 5 mg/kg once daily) stimulates host tumor immunity, reduces resident myeloid-derived suppressor cells within B16F10 tumors and synergizing with anti-programmed cell death protein-1 (PD-1, HY-P73361) to increase CD8+/regulatory T cell ratios within CT26 tumors[1]. Pharmacokinetic Parameters of Zamaporvint in Mice. [1] species Dose (i.v./p.o., mg/kg) Cmax (p.o., μM) C24 h (p.o., μM) AUCinf (p.o., μM.h) Cl (mL/min/kg) Vss (L/kg) F (p.o., %) T1/2 (hr) mouse 2/5 7.6 0.002 33.9 2.9 0.40 48 1.8 rat 2/5 3.6 0.009 10.5 5.8 0.64 31 2.5 dog 2/5 10.4 0.012 8.6 8.9 0.39 137 0.8

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References：

[1]. Phillips C, The Wnt Pathway Inhibitor RXC004 Blocks Tumor Growth and Reverses Immune Evasion in Wnt Ligand-dependent Cancer Models. Cancer Res Commun. 2022 Sep 2;2(9):914-928.  [Content Brief]