Frizzled
The Class F of the superfamily of G protein-coupled receptors (GPCRs) consists of Smoothened (SMO) and 10 FZD isoforms, FZD1–10. FZDs are ubiquitously expressed seven transmembrane (7TM) receptors that tightly regulate biological processes in multicellular organisms, ranging from embryonic development, stem cell regulation, organogenesis, cellular, and tissue polarity to tissue homeostasis. FZD signaling lies at the root of numerous pathologies for which treatments are limited. As cell-surface receptors, FZDs mediate responses induced by binding of secreted ligands of the Wingless/Int1 (WNT) family of proteins, of which 19 isoforms exist in mammals. In addition to WNTs, other proteins and structures have been identified as FZD ligands, such as Clostridium difficile toxin B and Norrin – the latter being selective for FZD4.
In mouse primary microglial cultures, WNT-5A induced GDP/GTP exchange on heterotrimeric G proteins, reduced cAMP levels, and induced G protein-mediated responses such as the mobilization of intracellular calcium, phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), microglial proliferation, invasion, and proinflammatory transformation. Interestingly, WNT-3A induced the expression of cyclooxygenase 2 (COX2), a classical target gene of the WNT/b-catenin pathway, through a pertussis toxin (PTX)-sensitive and ERK1/2-dependent pathway. FZDs and WNTs for the specification of intracellular signaling pathways in diverse cellular models and in vivo systems, but there is still a lack of understanding regarding the detailed mechanisms that govern ligand interaction, FZD activation, signal initiation, and signal specification.
References
1.Schulte G, et al. Trends Pharmacol Sci. 2018;39(9):828–842.
In mouse primary microglial cultures, WNT-5A induced GDP/GTP exchange on heterotrimeric G proteins, reduced cAMP levels, and induced G protein-mediated responses such as the mobilization of intracellular calcium, phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), microglial proliferation, invasion, and proinflammatory transformation. Interestingly, WNT-3A induced the expression of cyclooxygenase 2 (COX2), a classical target gene of the WNT/b-catenin pathway, through a pertussis toxin (PTX)-sensitive and ERK1/2-dependent pathway. FZDs and WNTs for the specification of intracellular signaling pathways in diverse cellular models and in vivo systems, but there is still a lack of understanding regarding the detailed mechanisms that govern ligand interaction, FZD activation, signal initiation, and signal specification.
References
1.Schulte G, et al. Trends Pharmacol Sci. 2018;39(9):828–842.
Wnt/Notch/Hedgehog
Frizzled
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Peptide Fz7-21
产品货号 : M16976
cas no: ——
Peptide Fz7-21 是一种有效的、选择性的 Frizzled 7 受体肽抑制剂,可抑制 HEK293 细胞中外源 WNT3A 刺激的 Wnt-β-catenin 信号传导,IC50 为 100 nM。 -
FzM1.8
产品货号 : M13514
cas no: 2204290-85-5
FzM1.8 是一种小分子卷曲受体 Fzd4 的变构激动剂,pEC50 为 6.4。 -
FzM1
产品货号 : M12565
cas no: 1680196-54-6
Frizzled4 (Fzd4) 受体的负变构调节剂和 Wnt/β-catenin 通路抑制剂,用于抑制 Wnt 拮抗作用,pEC50 值为 5.74。 -
NSC654259
产品货号 : M12087
cas no: 150068-95-4
一种新型小分子 Wnt 信号传导抑制剂,针对 Frizzled 富含半胱氨酸的结构域。 -
SRI 37892
产品货号 : M10150
cas no: 1030769-75-5
SRI 37892 (SRI37892) 是一种新型有效的小分子 Frizzled 7 (Fzd 7) 抑制剂,在 Wnt/β-catenin 测定中 IC50 为 0.66 uM。