Siremadlin

MDM2-p53蛋白质-蛋白质相互作用抑制剂(IC50=0.21nM)；在TR-FRET测定中，选择性抑制MDM2-p53蛋白质-蛋白质相互作用，而非MDM4-p53、YAP1-TEAD4、PCSK9-LDLR和Bcl-2-Bak相互作用（IC50s分别为3.3、>150、>50和>50µM）；抑制SJSA-1细胞生长(GI50=38nM)；在100nM时诱导SJSA-1细胞凋亡；在SJSA-1大鼠异种移植模型和HSAX2655 PDX大鼠脂肪肉瘤模型中诱导肿瘤消退并防止肿瘤再生，剂量为27mg/kg。A MDM2-p53 protein-protein interaction inhibitor (IC50 = 0.21 nM); selectively inhibits the MDM2-p53 protein-protein interaction over MDM4-p53, YAP1-TEAD4, PCSK9-LDLR, and Bcl-2-Bak interactions in TR-FRET assays (IC50s = 3.3, >150, >50, and >50 µM, respectively); inhibits the growth of SJSA-1 cells (GI50 = 38 nM); induces apoptosis in SJSA-1 cells at 100 nM; induces tumor regression and prevents tumor regrowth in an SJSA-1 rat xenograft model and an HSAX2655 PDX rat liposarcoma model at 27 mg/kg.分子式C26H24Cl2N6O4分子量555.4ClC1=CC=C([C@@H]2N(C(C3=C2N(C(C)C)C(C4=CN=C(N=C4OC)OC)=N3)=O)C5=CC(Cl)=CN(C5=O)C)C=C1