SU6656 is a small-molecule indolinone that selectively inhibits Src, Yes, and Fyn at IC50 values of 0.28μM, 0.02μM, and 0.17μM, respectively [1]. SU6656 activated AMPK and increased the phosphorylation at Thr172, and inhibited the phosphorylation of Erk1/2[2]. SU6656 has been widely used to regulate insulin secretion in different species[3].
In vitro, SU6656 treatment for 72 hours significantly inhibited BaF3 cell proliferation with an IC50 value of 0.18µM[4]. Treatment with 100μM SU6656 for 72h significantly inhibited FRO cell viability and resulted in increased p21 protein levels in the cells[5]. Treatment with 5μM SU6656 for 72h resulted in a significant increase in both nuclear and cytoplasmic volumes of B lymphoma cells[6].
In vivo, SU6656 treatment (25mg/kg; every other day for 12 weeks; i.p.) significantly increased total body, tibial, and lumbar Bone mineral density (BMD) in skeletally mature mice, without affecting body weight[7]. Intraperitoneal injection of SU6656 at a dose of 3 mg/kg/ day for 20 consecutive days alleviated fibrosis and improved lung function in a silicosis mouse model[8].
References:
[1] Blake R A, Broome M A, Liu X, et al. SU6656, a selective src family kinase inhibitor, used to probe growth factor signaling[J]. Molecular and cellular biology, 2000, 20(23): 9018-9027.
[2] Ross F A, Hawley S A, Auciello F R, et al. Mechanisms of paradoxical activation of AMPK by the kinase inhibitors SU6656 and sorafenib[J]. Cell chemical biology, 2017, 24(7): 813-824. e4.
[3] Cheng H, Straub S G, Sharp G W G. Inhibitory role of Src family tyrosine kinases on Ca2+-dependent insulin release[J]. American Journal of Physiology-Endocrinology and Metabolism, 2007, 292(3): E845-E852.
[4] Mologni L, Rostagno R, Brussolo S, et al. Synthesis, structure–activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors[J]. Bioorganic & medicinal chemistry, 2010, 18(4): 1482-1496.
[5] Kim S H, Kang J G, Kim C S, et al. Inhibition of p21 and Akt potentiates SU6656-induced caspase-independent cell death in FRO anaplastic thyroid carcinoma cells[J]. Hormone and Metabolic Research, 2013, 45(06): 408-414.
[6] Dussault N, Simard C, Néron S, et al. Human B lymphocytes and non-Hodgkin's lymphoma cells become polyploid in response to the protein kinase inhibitor SU6656[J]. Blood Cells, Molecules, and Diseases, 2007, 39(1): 130-134.
[7] Thouverey C, Ferrari S, Caverzasio J. Selective inhibition of Src family kinases by SU6656 increases bone mass by uncoupling bone formation from resorption in mice[J]. Bone, 2018, 113: 95-104.
[8] Hao X, Jin Y, Zhang Y, et al. Inhibition of oncogenic src ameliorates silica-induced pulmonary fibrosis via PI3K/AKT pathway[J]. International Journal of Molecular Sciences, 2023, 24(1): 774.
SU6656是一种小分子吲哚酮类化合物，可选择性抑制Src、Yes和Fyn激酶活性，IC50值分别为0.28μM、0.02μM和0.17μM[1]。SU6656能激活AMPK并促进Thr172位点磷酸化，同时抑制Erk1/2的磷酸化[2]。SU6656已广泛应用于不同物种的胰岛素分泌调控研究[3]。
在体外，SU6656处理72小时可显著抑制BaF3细胞增殖，IC50值为0.18µM[4]。使用100μM的SU6656处理FRO细胞72小时，能显著抑制细胞活力并提高细胞内p21蛋白水平[5]。用5μM的SU6656处理B淋巴瘤细胞72小时，可显著增加细胞核与细胞质体积 [6]。
在体内，隔天腹腔注射25mg/kg剂量的SU6656连续12周，能显著增加骨骼成熟小鼠的全身、胫骨和腰椎骨密度(BMD)，且不影响体重[7]。连续20天每日腹腔注射3mg/kg/day剂量的SU6656，可减轻硅肺病小鼠模型的纤维化程度并改善肺功能[8]。