Pyrvinium pamoate

Pyrvinium pamoate is an FDA-approved antihelmintic drug that inhibits WNT pathway signaling. In Vitro: Pyrvinium pamoate (0-500 nM) inhibits proliferation of MCF-7 (luminal), MDA-MB-231 (claudin-low), MDA-MB-468 (basal-like) and SkBr3 (HER2-OE) cells in a dose-dependent manner, with IC₅₀ value of 1170±105.0 nM against MDA-MB-231 cell line. Pyrvinium pamoate significantly inhibits self-renewal and proliferation of BCSCs, and suppresses BCSC population with a distinct phenotype. Pyrvinium pamoate significantly decreases average expression levels of FZD1, FZD10, WNT1, WNT7B, CTNNB1, MYC, and LRP5 at transcriptional level. Moreover, Pyrvinium pamoate also efficiently down-regulates the expression of other stemness genes including ALDH1, CD44 and ABCG2^[1]. Pyrvinium pamoate blocks colon cancer cell growth in vitro in a dose-dependent manner with great differences in the inhibitory concentration (IC₅₀), ranging from 0.6 to 65 μM for colon cancer cells with mutations in WNT signaling. Pyrvinium pamoate decreases messenger RNA (mRNA) and protein levels of known WNT target genes as c-MYC and thereby led to the induction of p21^[2]. Pyrvinium pamoate ultimately inhibits Wnt signalling despite its lack of efficacy on CK1^[3]. Pyrvinium pamoate imposes specific toxicity on cardiac fibroblasts in ischemia (IC₅₀=9.5 nM). The cytotoxic effect of Pyrvinium pamoate on cardiac fibroblasts specifically under glucose- and glutamine-deficient condition^[4]. In Vivo: In the xenograft model, Pyrvinium pamoate (500 nM)-pretreatment strongly delays tumor size and tumor weight, and the tumor volume is markedly decreased^[1].