sw-100

SW-100 是一种选择性组蛋白去乙酰化酶 6 抑制剂，IC50为2.3 nM。它有提高的穿过血脑屏障的能力，相对于其他 HDAC 同工酶，还显示出对 HDAC6 的至少高 1000 倍的选择性。

CDK8-IN-20 (Compound 67j) 是一种口服有效的高选择性 I 型CDK8 抑制剂，IC50值为 70.5 nM。针对CDK19、CDK7和CDK9的IC50值分别为147.8、726.9 和 217.4 nM。该化合物能抑制 HCT-116、HT-29 和 SW-480 细胞增殖，IC₅₀值分别为 5.9、17.93 和 9.52 μM，并对正常胃黏膜上皮细胞 GES-1 的细胞毒性较低 (IC50大于 100 μM)。此外，CDK8-IN-20 抑制Wnt/β-catenin通路，下调β-catenin、Cyclin D1和c-Myc的表达，诱导活性氧 (ROS) 的产生，并导致 G2/M 期和 S 期阻滞，它可用于包括结肠癌在内的癌症研究。

SAR502250 is a potent, selective, ATP competitive, orally active and brain-penetrant inhibitor of GSK3, with an IC50 of 12 nM for human GSK-3β. SAR502250 displays antidepressant-like activity. SAR502250 can be used for the research of Alzheimer’s disease (AD)[1][2]. SAR502250 (0.01-1 μM; 36 h) attenuates the Aβ25-35-induced cell death in rat embryonic hippocampal neurons[2]. SAR502250 (1-100 mg/kg; a single p.o,) attenuates tau hyperphosphorylation in the cortex and spinal cord of transgenic mice expressing P301L tau[2].SAR502250 (10-30 mg/kg; p.o. once daily for 7 weeks) improves the cognitive deficit in transgenic APP(SW)/Tau(VLW) mice after infusion of Aβ25-35[2].SAR502250 (10-30 mg/kg; a single p.o.) significantly increases the percentage of lever-presses in the inter-response time (IRT) bin (49-96 s), with a significant augmentation of the percentage of reinforced responses[2].SAR502250 (30 mg/kg; i.p. once daily for 28 d) ameliorates chronic stress-induced degradation of the physical state of the mice coat[2].SAR502250 (10-60 mg/kg; a single p.o.) decreases hyperactivity produced by psychostimulantsin mice[2]. [1]. Fukunaga K, et, al. 2-(2-Phenylmorpholin-4-yl)pyrimidin-4(3H)-ones; a new class of potent, selective and orally active glycogen synthase kinase-3β inhibitors. Bioorg Med Chem Lett. 2013 Dec 15;23(24):6933-7.[2]. Griebel G, et, al. The selective GSK3 inhibitor, SAR502250, displays neuroprotective activity and attenuates behavioral impairments in models of neuropsychiatric symptoms of Alzheimer’s disease in rodents. Sci Rep. 2019 Dec 2;9(1):18045.