FGTI-2734

FTase和GGTaseI的双重抑制剂（IC50分别为250和520nM）；抑制致癌H-Ras转化的NIH3T3细胞中的H-Ras和Rap1A的异戊烯化（IC50分别为88.7和2,700nM）；在10和30µM时抑制MIA PaCa-2和H460癌细胞中K-Ras的膜定位；在每天50和100mg/kg的剂量下，在表达突变型KRAS的胰腺癌的PDX小鼠模型中，减少肿瘤生长，增加肿瘤内p53的表达，诱导肿瘤内细胞凋亡，并降低肿瘤内HDJ2法呢基化和Rap1A香叶基香叶基化。A dual inhibitor of FTase and GGTase I (IC50s = 250 and 520 nM, respectively); inhibits prenylation of H-Ras and Rap1A (IC50s = 88.7 and 2,700 nM, respectively) in oncogenic H-Ras-transformed NIH3T3 cells; inhibits membrane localization of K-Ras in MIA PaCa-2 and H460 cancer cells at 10 and 30 µM; reduces tumor growth, increases intratumoral expression of p53, induces intratumoral apoptosis, and decreases intratumoral HDJ2 farnesylation and Rap1A geranylgeranylation in PDX mouse models of mutant KRAS-expressing pancreatic cancer at 50 and 100 mg/kg per day.分子式C26H31FN6O2S分子量510.6N#CC1=CC=C(N(CCN(S(=O)(C2=CC=CC=N2)=O)CC3CCCCC3)CC4=CN=CN4C)C(F)=C1