PHT427 是一种Akt和PDPK1双重抑制剂，与 Akt 和 PDPK1 中的 PH 结构域有亲和性，Ki分别为 2.7 μM 和 5.2 μM。
产品描述
PHT-427 is a dual Akt (Ki: 2.7 μM) and PDPK1 (Ki: 5.2 μM) inhibitor (high-affinity binding for the PH domains of Akt and PDPK1).
体外活性
作用于BxPC-3时,PHT-427（125-250 mg/kg）对肿瘤生长的抑制率达到80%.作用于BxPC-3 胰腺癌, MCF-7 乳腺癌和A-549 NSCL癌移植瘤时,PHT-427具有明显的抗肿瘤活性.
体内活性
作用于Panc-1细胞时,PHT-427具有抗增殖效果（IC50：65 μM）。作用于PC-3前列腺癌细胞时,PH-427（10 μM）使p-Ser241-PDPK1和p-Thr308-Akt显著降低,说明PHT-427可抑制 Akt 和PDKP1。作用于质膜时, PHT-427也抑制Akt 和PDKP1 PH 域易位。PHT-427诱导凋亡,并抑制AKT磷酸化,主要发生在Ser473残基,较少发生在 Thr308 残基（IC50：6.3 μM）, 对全部AKT 蛋白表达无影响。
激酶实验
Surface plasmon resonance (SPR) spectroscopy binding assays: All interaction analyses are performed with a Biacore 2000, Biacore 2000 Control Software v3.2, and BIAevaluation v4.1 analysis software. The PH domain GST-fusion proteins (Akt1, IRS1, and PDK1) are immobilized on a CM5 Sensorchip using Biacore's Amine Coupling Kit to a level of 10,000 Response units (RUs). Small molecule analytes at concentrations ranging from 0.1 to 10 × the predicted KD are injected at a high flow rate (30μL/min). DMSO concentrations in all samples and running buffer are 1% (v/v) or less.
Cas No.
1191951-57-1
分子式
C20H31N3O2S2
分子量
409.61
别名
CS-0223;PHT 427
储存和溶解度
DMSO:41 mg/mL (100 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years
