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    SB 216763是一種強效、選擇性且ATP競爭性的GSK-3抑制劑，顯著作用于GSK-3α和GSK-3β，其IC50僅為34.3 nM[1-3]。

SB 216763(1-20μM;24h) 呈劑量依賴性誘導(dǎo)β-catenin介導(dǎo)的轉(zhuǎn)錄。此外，SB 216763(10、15和20μM)在小鼠胚胎成纖維細胞(MEF)培養(yǎng)時，可以在缺乏外源性白血病抑制因子(LIF)的情況下維持小鼠胚胎干細胞(mESCs)的多能狀態(tài)[4]。SB 216763促進神經(jīng)發(fā)生，但不改變細胞周期退出或細胞存活[5]。

SB 216763（1-1.5 mg/kg/day；4weeks；s.c）能夠逆轉(zhuǎn)醛固酮(Aldo)注射引起的心臟和腎臟炎癥和纖維化分子標志物的表達水平升高。此外，SB 216763(10 mg/kg；i.p;3weeks)有效抑制心臟和腎臟炎癥細胞因子水平，包括TNF-a、IL-1β和MCP-1[6]。SB 216763可降低高脂飲食(HFD)誘導(dǎo)的肥胖/ 2型糖尿病(T2D)雌性小鼠胃排空延遲(DGE) [7]。在使用安非他明之前使用SB 216763 (2.5-5 mg/kg, i.p.)進行預(yù)處理可顯著降低安非他明引起的活動和刻板行為[8]。

產(chǎn)品性質(zhì)：

Cas No.:280744-09-4

化學名:3-(2,4-dichlorophenyl)-4-(1-methylindol-3-yl)pyrrole-2,5-dione

Canonical SMILES:CN1C=C(C2=CC=CC=C21)C3=C(C(=O)NC3=O)C4=C(C=C(C=C4)Cl)Cl

分子式:C19H12Cl2N2O2

分子量:371.22

溶解度:≥ 56.8mg/mL in DMSO

儲存條件：Store at -20°C

注意事項：

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References:

[1]. Wang M, Gao M, et,al. The first synthesis of [(11)C]SB-216763, a new potential PET agent for imaging of glycogen synthase kinase-3 (GSK-3). Bioorg Med Chem Lett. 2011 Jan 1;21(1):245-9. doi: 10.1016/j.bmcl.2010.11.026. Epub 2010 Nov 11. PMID: 21115250.

[2]. Coghlan MP, Culbert AA, et,al. Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription. Chem Biol. 2000 Oct;7(10):793-803. doi: 10.1016/s1074-5521(00)00025-9. PMID: 11033082.

[3]. Xu Y, Zhao J, et,al.Derivation of totipotent-like stem cells with blastocyst-like structure forming potential. Cell Res. 2022 Jun;32(6):513-529. doi: 10.1038/s41422-022-00668-0. Epub 2022 May 4. PMID: 35508506; PMCID: PMC9160264.

[4]. Kirby LA, Schott JT, et,al.Glycogen synthase kinase 3 (GSK3) inhibitor, SB-216763, promotes pluripotency in mouse embryonic stem cells. PLoS One. 2012;7(6):e39329. doi: 10.1371/journal.pone.0039329. Epub 2012 Jun 26. PMID: 22745733; PMCID: PMC3383737.

[5]. Lange C, Mix E, et,al. Small molecule GSK-3 inhibitors increase neurogenesis of human neural progenitor cells. Neurosci Lett. 2011 Jan 13;488(1):36-40. doi: 10.1016/j.neulet.2010.10.076. Epub 2010 Nov 5. PMID: 21056624.

[6]. Zhang YD, Ding XJ, et,al. SB-216763, a GSK-3β inhibitor, protects against aldosterone-induced cardiac, and renal injury by activating autophagy. J Cell Biochem. 2018 Jul;119(7):5934-5943. doi: 10.1002/jcb.26788. Epub 2018 Mar 30. PMID: 29600538; PMCID: PMC6001754.

[7]. Sampath C, Srinivasan S, et,al.Inhibition of GSK-3β restores delayed gastric emptying in obesity-induced diabetic female mice. Am J Physiol Gastrointest Liver Physiol. 2020 Oct 1;319(4):G481-G493. doi: 10.1152/ajpgi.00227.2020. Epub 2020 Aug 19. PMID: 32812777; PMCID: PMC7654647.

[8]. Enman NM, Unterwald EM. Inhibition of GSK3 attenuates amphetamine-induced hyperactivity and sensitization in the mouse. Behav Brain Res. 2012 May 16;231(1):217-25. doi: 10.1016/j.bbr.2012.03.027. PMID: 22649795; PMCID: PMC3566781.