GA-017 is a selective and potent small-molecule inhibitor of LATS1 and LATS2 kinases, with IC50 values of 4.10 ± 0.79nM for LATS1 and 3.92 ± 0.42nM for LATS2, respectively[1]. GA-017 is typically used for research in 3D cell culture systems, organoid expansion, and Hippo signaling pathway modulation[1][2].
GA-017 (1 - 20μM, 1 - 6h) inhibited the phosphorylation of YAP/TAZ in a dose-dependent manner under both 2D and 3D culture conditions and the inhibitory effect of GA-017 continued for 6h in SKOV3 cells[1]. GA-017 (10μM, 7 days) visibly increased both cell aggregate size and total cell number in the BCE C/D-1b cells[3].
GA-017 (2.5mg/kg/day, 4 weeks, i.p.) significantly decreased the body weight of mice while notably increasing tumor weight and size in the Ferredoxin 1 (FDX1)-knockdown colorectal cancer mouse model. GA-017 (2.5mg/kg/day, 4 weeks, i.p.) significantly increased the number of Ki67-positive cells in the FDX1-knockdown colorectal cancer mouse model. GA-017 (2.5mg/kg/day, 4 weeks, i.p.) significantly suppressed the production of pyruvate and α-ketoglutarate in the FDX1-knockdown colorectal cancer mouse model[4].
References:
[1] Aihara A, Iwawaki T, Abe-Fukasawa N, et al. Small molecule LATS kinase inhibitors block the Hippo signaling pathway and promote cell growth under 3D culture conditions[J]. Journal of Biological Chemistry, 2022, 298(4): 101779.
[2] Xu Z, Xu X, Mi Y, et al. Identifying the Role of YAP in the Development of Rumen Epithelium Using 3D Organoid[J]. Stem Cells International, 2025, 2025(1): 5105796.
[3] Abe-Fukasawa N, Hayashi R, Morita M, et al. Ex vivo expansion of corneal endothelial cells enabled by small molecule inhibitors of LATS kinase[J]. Regenerative Therapy, 2025, 30: 730-739.
[4] Hu Y, Liu H, Tan X, et al. Knocking down ferredoxin 1 inhibits the progression of colorectal Cancer and regulates Cuproptosis via mediating the Hippo signaling pathway[J]. Molecular Carcinogenesis, 2025, 64(5): 911-922.
GA-017是一种选择性、强效的LATS1和LATS2激酶小分子抑制剂，其对LATS1和LATS2的IC50值分别为4.10 ± 0.79nM和3.92 ± 0.42nM[1]。GA-017通常用于3D细胞培养系统、类器官扩增和Hippo信号通路调节的研究[1][2]。
在2D和3D培养条件下，GA-017（1 - 20μM，1 - 6h）以剂量依赖性方式抑制YAP/TAZ的磷酸化，并且GA-017在SKOV3细胞中的抑制作用持续6h[1]。GA-017（10μM，7天）明显增加了BCE C/D-1b细胞中的细胞聚集体大小和细胞总数[3]。
在铁氧还蛋白1（FDX1）敲低结直肠癌小鼠模型中，GA-017（2.5mg/kg/天，4周，腹腔注射）显著降低小鼠体重，同时显著增加肿瘤重量和大小。GA-017（2.5mg/kg/天，4周，腹腔注射）显著增加了FDX1敲低结直肠癌小鼠模型中Ki67阳性细胞的数量。GA-017（2.5mg/kg/天，4周，腹腔注射）显著抑制FDX1敲低结直肠癌小鼠模型中丙酮酸和α-酮戊二酸的产生[4]。