Wnt3a

Zamaporvint (RXC004) 是一种具有选择性、口服活性和有效性的 Wnt 途径抑制剂，作用于膜结合脂肪酰转移酶 Porcupine，阻断 Wnt 配体棕榈酰化、分泌及通路活化。Zamaporvint 在多种癌细胞系中显示出抗肿瘤和抗增殖活性。

Ipivivint, a first-in-class, orally active and potent CDC-like kinase (CLK) inhibitor, inhibits CLK1 (IC50=1.4 μM), CLK2 (IC50=0.002 μM) and CLK3 (IC50=0.022 μM). Ipivivint reduces Wnt pathway signaling gene expression through inhibiting CLK activity and serine and arginine rich splicing factor (SRSF) phosphorylation and disrupting spliceosome activity. Ipivivint can be used for the research of cancer[1]. Ipivivint (SW480 cells; 0.01~10 μM; 1 hour) potently inhibits SRSF5 6 phosphorylation[1].Ipivivint (SW480 cells; 0.03 μM~3 μM; 48 hour) induced apoptosis[1]..Ipivivint (HEK-293T cells; 0.03 μM~3 μM; 1 hour) inhibits Wnt β-catenin signaling induced by Wnt3a[1].Ipivivint (SW480 cells; 0.3~10 μM; 6 hour) increases nuclear speckle enlargement[1].Ipivivint (SW480 cells; 0.3~3μM; 24hours) significantly decreases expression of Wnt target genes (AXIN2, LEF1, MYC, and TCF7) and TCF7L2. SM08502 (SW480 cells; 0.03~3μM; 24hours) inhibits cytoplasmic or nuclear fractions protein expression. Ipivivint (NCI-N87 cells) inhibits proliferation[1].Ipivivint strongly inhibits Wnt pathway signaling activity (EC50 = 0.046 μM) in SW480 colon cancer cells[1]. Ipivivint (25 mg kg; p.o.) potently inhibits tumor SRSF6 phosphorylation[1]. [1]. Tam BY, et al. The CLK inhibitor SM08502 induces anti-tumor activity and reduces Wnt pathway gene expression in gastrointestinal cancer models. Cancer Lett. 2020;473:186-197.

Palmitoleic acid alkyne, an ω-terminal alkyne derivative of palmitoleic acid, facilitates click chemistry applications. This compound has played a crucial role in examining protein palmitoylation processes. Specifically, the cis form of palmitoleic acid alkyne selectively tags wild-type Wnt3a protein within mouse fibroblast L-cells expressing Wnt3a and its secretion in conditioned media, distinguishing itself from the trans form and proving ineffective against the S209A mutant Wnt3a.

Fz7-21 ((Ac)-LPSDDLEFWCHVMY-NH2) 是一种 Frizzled 7 (FZD 7) 受体的肽抑制剂，能够选择性的与FZD7 CRD 亚类结合。它还阻断了WNT3A 介导的β-catenin 在小鼠L 细胞中的稳定作用。它对外源性WNT3A 刺激和转染WNT3A 或WNT1的HEK293细胞Wnt β-catenin 信号传导有损伤。

FZD7 antagonist 1 (peptide 34), a dFz7-21 analogue, inhibits wnt3a with an IC50 of 9.2 nM and blocks TcdB−FZD interaction by targeting FZD receptors [1].