Zamaporvint

SKU: orb1944711

Description

Zamaporvint (RXC004) is a potent, orally bioavailable porcupine inhibitor that suppresses Wnt signaling by blocking Wnt ligand palmitoylation and secretion. It has demonstrated anti-proliferative effects across diverse cancer cell lines in vitro and has shown anti-tumor activity in preclinical in vivo models.

Research Area

Metabolism Research, Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 1900754-56-4
• MW: 439.39
• Purity: 99.34% (May vary between batches)
• Formula: C₂₁H₁₆F₃N₇O
• SMILES: O=C(NC1=NC=C(C=C1)C=2N=CC=NC2)CN3C=NC(C=4C=CN=C(C4)C(F)(F)F)=C3C
• Target: Wnt/beta-catenin,Others,Acyltransferase,Porcupine
• Solubility: DMSO:100 mg/mL (227.59 mM)

Bioactivity

• Target IC50:
  L-wnt3a cells:64 pM
• In Vivo:
  Zamaporvint, administered orally at doses of 1.5 mg/kg or 5 mg/kg twice daily, or 5 mg/kg once daily for 28 days, has demonstrated the ability to reduce tumor growth. In ligand-dependent SNU-1411, AsPC1, and HPAF II models with observable inhibition of Wnt-responsive gene expression (including cMyc), as well as in Wnt ligand-independent HCT116 xenograft models, tumor growth remained unaffected.At a dose of 1.5 mg/kg and 5 mg/kg once daily, Zamaporvint reduced the number of Ki67-positive cells in the overall tumor area, with a more pronounced effect in the differentiated tumor regions. Its anti-tumor effects were observed in the B16F10 "cold" tumor model through the inhibition of immune evasion.Zamaporvint, at doses of 1.5 or 5 mg/kg once daily, stimulated the host tumor immune response by decreasing bone marrow-derived suppressor cells within B16F10 tumors. It also exhibited a synergistic effect with anti-programmed cell death protein-1 (PD-1) to increase the proportion of regulatory T cells (CD8+/CT26) within the tumor.
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• In Vitro:
  Treatment of L-wnt3a cells with Zamaporvint (300 nM, 48 h) dose-dependently reduced the ability to activate β-catenin responsive luciferase reporter gene in conditioned medium, with an IC50 of 64 pM. The addition of recombinant Wnt3a restored luciferase activity, indicating no impact on downstream Wnt signaling transduction.The impact of Zamaporvint (100 nM, 24 h) on proliferation reflected a concentration-dependent downregulation of c-Myc mRNA. There was a decrease in the proportion of cells in the S phase, and a strong inhibition of the expression of mitotic marker phosphorylated histone-H3 in cells with aberrant upstream Wnt pathway components, suggesting cell cycle arrest. Additionally, an additive effect was observed at the same dose, revealing a reduction in its immunosuppressive properties after administration.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Wnt, RXC 004, RXC004, RXC-004, Zamaporvint

Compound Identifiers

PubChem CID

121273514