gsk3-in-1

GSK3-IN-1是一种 GSK3B-糖原合酶激酶3β抑制剂。

CDKL5 GSK3-IN-1 (Compound 2) 是一种有效且具有选择性的CDKL5 GSK3化学探针。它能强效抑制CDKL5和GSK3α β，在NanoBRET测定中的IC50值分别为4.6 nM（CDKL5）、24 nM（GSK3β）和9.5 nM（GSK3α）。CDKL5 GSK3-IN-1 适用于中枢神经系统疾病的研究。

CDK9 10 GSK3β-IN-1 是一种激酶抑制剂 (Flavopiridol 类似物)，能有效抑制 HsGSK3β、HsCDK9 CyclinT、HsCDK5 p25 和 HsCDK2 CyclinA，其 IC50 值分别为 59 nM、64 nM、1.093 μM 和 1.725 μM。CDK9 10 GSK3β-IN-1 表现出相当或高于 Flavopiridol 的抗癌细胞活性，在体外对多达七种癌细胞系表现出高抗增殖活性。

AChE GSK-3β-IN-1 是一种有效的、能透过血脑屏障的双重AChE GSK-3β抑制剂，能够作用于 hAChE (IC50: 1.2 nM)、hBChE (IC50: 149.8 nM) 和 hGSK-3β (IC50: 22.4 nM)。AChE GSK-3β-IN-1 能够占据 DYRK1A 的 ATP 结合位点。AChE GSK-3β-IN-1 对 CMGC 激酶家族表现出较高的激酶选择性。AChE GSK-3β-IN-1 能够抑制 ROS 表达，减少氧化应激。AChE GSK-3β-IN-1 能够用于研究阿尔兹海默症。

GSK3-IN-4是一种 GSK-3抑制剂，对 GSK-3α和 GSK-3β的IC50值为 0.101-1 μM。

GSK3-IN-2 是一种有效的 GSK3抑制剂。

API-1 (NSC-177223) 是Akt PKB 抑制剂，可同 PH 结构域相结合并抑制 Akt 膜易位，有效降低 Akt 的磷酸化水平。它可选择性的抑制PKB，对 PKC 和 PKA 的激活无抑制作用。它可以和 TNF 相关的凋亡诱导配体协同作用从而诱导细胞凋亡。

GSK-3 CDK5 CDK2-IN-1 is an imidazole derivative compound that inhibits cdk5, cdk2, and GSK-3.it has demonstrated applications in cancer research and the study of neurodegenerative diseases [1].

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.

Potent and selective CLK inhibitor (IC50 values are 28, 88 and 510 nM for CLK4, 1 and 2, respectively). Exhibits no significant activity at CLK3, DYRK, CDK or GSK3 at a concentration of 10 μM. Inhibits growth of a range of cancer cell lines in vitro at subnanomolar concentrations. Walter et al (2018) Molecular structures of cdc2-like kinases in complex with a new inhibitor chemotype. PLoS One 13 e0196761 PMID:29723265

6-Me-ATP（N6-Methyl-ATP）为ATP的N6修饰衍生物。该化合物与GSK3β结合亲和力显著，能有效作为GSK3β催化底物肽磷酸化的磷酸基团供体。

6-Me-ATP trisodium (N6-Methyl-ATP) 是N6-修饰的ATP衍生物，展现对GSK3良好的结合亲和力，可作为GSK3β磷酸化底物肽的磷酸基团供体。

Antitrypanosomal agent 14（Compound 1）是一种针对T. brucei的有效抑制剂，其EC50为0.47 μM。它对TbGSK3的抑制作用表现在IC50为12 μM。该化合物主要用于非洲人类锥虫病的研究。

PT-65是一种高效且具选择性的GSK3降解剂，对SH-SY5Y细胞中的GSK3α(DC50=28.3 nM)和GSK3β(DC50=34.2 nM)表现出最强的降解活性。该化合物主要用于研究阿尔茨海默病。