| Description |
Wnt-C59 (C59) is a highly potent and oral porcupine (PORCN) inhibitor with an IC50 of 74 pM.
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| Related Catalog |
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| Target |
IC50: 74 pM (PORCN)[1]
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| In Vitro |
Wnt-C59 (C59) inhibits PORCN activity in vitro at nanomolar concentrations, as assessed by inhibition of Wnt palmitoylation, Wnt interaction with the carrier protein Wntless/WLS, Wnt secretion, and Wnt activation of β-catenin reporter activity. Wnt-C59 inhibits WNT3A-mediated activation of a multimerized TCF-binding site driving luciferase with an IC50 of 74 pM[1].
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| In Vivo |
Wnt-C59 displays good bioavailability in mice. Wnt-C59 blocks progression of mammary tumors in MMTV-WNT1 transgenic mice while downregulating Wnt/β-catenin target genes[1]. Wnt-C59 has the potential to eradicate cancer stem cells in human tumors. Wnt-C59 inhibits stemness properties of NPC cells in a dosage-dependent manner by arresting sphere formation in both HNE1 and SUNE1 cells[2].
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| Cell Assay |
1×104 HK1, CNE1, HNE1 and SUNE1 cells are seeded in 24-well plates, and Wnt-C59 (5 μM, 10 μM, and 20 μM) is added the next day. Cell confluence is determined by microscopy at 24, 48, 72, and 96 hours after seeding of cells. The IC50 is determined by MTT assay[2].
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| Animal Admin |
Mice[1] Female nude mice orthotopically transplanted with independent MMTV-WNT1 tumors are treated with vehicle or Wnt-C59 10 mg/kg once daily for 17 days. Tumor volumes are measured on alternate days[1].
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| References |
[1]. Proffitt KD, et al. Pharmacological inhibition of the Wnt acyltransferase PORCN prevents growth of WNT-driven mammary cancer. Cancer Res. 2013 Jan 15;73(2):502-7. [2]. Cheng Y, et al. Wnt-C59 arrests stemness and suppresses growth of nasopharyngeal carcinoma in mice by inhibiting the Wnt pathway in the tumor microenvironment. Oncotarget. 2015 Jun 10;6(16):14428-39.
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