N-(4-ベンジルピペラジン-1-イル)-1-(3,5-ジメチル-1-フェニル-1H-ピラゾール-4-イル)メタンイミン

外観

白色〜黄色, 結晶〜粉末

溶解性

メタノールに溶ける。

説明

Smoothened (SMO) is a GPCR-like receptor which, with Patched, mediates hedgehog signaling to regulate gene expression through the Gli transcription factors. SANT 1 is a potent inhibitor of hedgehog signaling that acts by directly antagonizing SMO (IC₅₀ = 20 nM). It counteracts SMO activation by the SMO agonist SAG but only partially competes with SAG binding to SMO. SANT 1 targets inactive SMO while it is in the cytoplasm, before it relocates to the primary cilium and is activated. Through antagonism of SMO, SANT 1 represses Gli-mediated transcription in a variety of cell types.

化学的特性

Pale Yellow Solid

使用

Treatment of Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma cells² and chronic lymphocytic leukemia cells³ with SANT-1 induced cell death.

生物活性

Potent, cell-permeable inhibitor of Sonic hedgehog (Shh) signaling; high affinity antagonist of smoothened activity (K D = 1.2 nM). Inhibits smoothened agonist effects with an IC 50 of 20 nM (in Shh-LIGHT2 cells).