GGTI298 is a selective, irreversible inhibitor of geranylgeranyl transferase I (GGTase-I) (IC50 = 3μM) [1]. By inhibiting GGTase-I, GGTI298 blocks geranylgeranylation of small GTPases such as RhoA, leading to cell cycle arrest at the G0/G1 phase and induction of apoptosis [2-3]. GGTI298 is primarily used to treat non-small cell lung cancer [4].
In A549 cells, Gefitinib and GGTI298 (2.5-5µM; 48h) have synergistic anti-proliferative effects on cells [5]. In A549 cells, GGTI298 (15µM; 48h) induces cell apoptosis [6].
In Luc-G33 cells xenograft mice model, combination treatment with Zoledronate and GGTI298 (1.16mg/kg; sc; 35d) both reduced tumor growth [7].
References:
[1]. Dan H C, Jiang K, Coppola D, et al. GGTI 298[J]. Oncogene, 2004, 23: 706-715.
[2]. Peterson Y K, Kelly P, Weinbaum C A, et al. A novel protein geranylgeranyltransferase-I inhibitor with high potency, selectivity, and cellular activity[J]. Journal of Biological Chemistry, 2006, 281(18): 12445-12450.
[3]. Vogt A, Sun J, Qian Y, et al. The geranylgeranyltransferase-I inhibitor GGTI-298 arrests human tumor cells in G0/G1 and induces p21WAF1/CIP1/SDI1 in a p53-independent manner[J]. Journal of Biological Chemistry, 1997, 272(43): 27224-27229.
[4]. Chen S, Fu L, Raja S M, et al. Dissecting the roles of DR4, DR5 and c-FLIP in the regulation of geranylgeranyltransferase I inhibition-mediated augmentation of TRAIL-induced apoptosis[J]. Molecular cancer, 2010, 9(1): 23.
[5]. Liu B S, Dai X Y, Xia H W, et al. Geranylgeranyl transferase 1 inhibitor GGTI-298 enhances the anticancer effect of gefitinib[J]. Molecular Medicine Reports, 2018, 18(4): 4023-4029.
[6]. Miquel K, Pradines A, Sun J, et al. GGTI-298 induces G0-G1 block and apoptosis whereas FTI-277 causes G2-M enrichment in A549 cells[J]. Cancer research, 1997, 57(10): 1846-1850.
[7]. Lau C P Y, Wong K C, Huang L, et al. A mouse model of luciferase-transfected stromal cells of giant cell tumor of bone[J]. Connective tissue research, 2015, 56(6): 493-503.
GGTI298是一种选择性、不可逆的香叶基香叶酰转移酶I（GGTase-I）抑制剂（IC50 = 3μM) [1]。通过抑制GGTase-I，GGTI298可阻断RhoA等小GTP酶的香叶基香叶酰化修饰，导致细胞周期停滞于G0/G1期并诱导细胞凋亡 [2-3]。GGTI298主要用于治疗非小细胞肺癌 [4]。
在A549细胞中，gefitinib和GGTI298（2.5-5μM；48h）具有协同抗增殖作用 [5]。在A549细胞中，GGTI298（15μM；48h）可诱导细胞凋亡 [6]。
在Luc-G33细胞异种移植小鼠模型中，zoledronate和GGTI298（1.16mg/kg；sc；35d）联合治疗均能降低肿瘤增长 [7]。