同义名 :	AGI-1067; Probucol monosuccinate; AGZ1067. Probucol monosuccinae.; AGZ-1067
	CAS号 :	216167-82-7
	货号 :	A708788
	分子式 :	C35H52O5S2
	纯度 :	99%+
	分子量 :	616.91
	MDL号 :	MFCD08690469
	存储条件：	Pure form Sealed in dry, 2-8°C In solvent -20°C:3-6个月-80°C:12个月
	溶解度 :	-
	动物实验配方：

生物活性

描述

AGI-1067 is a novel ASK1 inhibitor. It improves AGE‐induced cardiac dysfunction by inhibiting MKKs/p38 MAPK and NF‐κB apoptotic signaling. Administration of AGI-1067 at dose of 50-150mg/kg, i.p., inhibited the activation of MKKs/p38 MAPK by inhibiting the disassociation of ASK1 and Trx1, which suppressed the AGE‐induced myocyte apoptosis[1]. AGI-1067 is a novel, phenolic, intra- and extracellular antioxidant that inhibits the expression of a number of proinflammatory genes involved in atherosclerosis. It is the metabolically stable monosuccinic acid ester of probucol representing a novel class of orally bioavailable compounds termed vascular protectants. AGI-1067 also exhibits mild antiplatelet properties inhibiting surface expression of various key platelet receptors, the formation of platelet monocyte microparticles and PAR-1 thrombin receptors[2]. AGI-1067 lowered low-density lipoprotein cholesterol (LDLc) by 41 and 90% at oral doses of 50 and 150 mg/kg, respectively and increased high-density lipoprotein cholesterol (HDLc) by 107% at the higher dose. At the cellular level, AGI-1067 inhibited tumor necrosis factor-alpha-inducible expression of VCAM-1, MCP-1, and E-selectin in human aortic endothelial cells (IC50 values = 6, 10, and 25 μM, respectively)[3]. In addition, AGI-1067 reduces H(b)A1c, improves fasting plasma glucose, and reduces new-onset diabetes. Pretreatment with 10 μM AGI-1067 increased glucose-stimulated insulin secretion (11 mM) without affecting secretion in basal (3mM) glucose. AGI-1067 enhanced the intracellular calcium response to glucose stimulation in 7mM and 11mM glucose, but had no effect in 28mM or basal glucose[4].

实验方案
	1mg	5mg	10mg
1 mM 5 mM 10 mM	1.62mL 0.32mL 0.16mL	8.10mL 1.62mL 0.81mL	16.21mL 3.24mL 1.62mL

参考文献

[1]Liu Z, Zheng S, Wang X, Qiu C, Guo Y. Novel ASK1 inhibitor AGI-1067 improves AGE-induced cardiac dysfunction by inhibiting MKKs/p38 MAPK and NF-κB apoptotic signaling. FEBS Open Bio. 2018 Aug 17;8(9):1445-1456 [2]Serebruany VL, Malinin A, Eisert C, Ong S. AGI-1067, a novel vascular protectant, anti-inflammatory drug and mild antiplatelet agent for treatment of atherosclerosis. Expert Rev Cardiovasc Ther. 2007 Jul;5(4):635-41. [3]Sundell CL, Somers PK, Meng CQ, Hoong LK, Suen KL, Hill RR, Landers LK, Chapman A, Butteiger D, Jones M, Edwards D, Daugherty A, Wasserman MA, Alexander RW, Medford RM, Saxena U. AGI-1067: a multifunctional phenolic antioxidant, lipid modulator, anti-inflammatory and antiatherosclerotic agent. J Pharmacol Exp Ther. 2003 Jun;305(3):1116-23. [4]Crim WS, Wu R, Carter JD, Cole BK, Trace AP, Mirmira RG, Kunsch C, Nadler JL, Nunemaker CS. AGI-1067, a novel antioxidant and anti-inflammatory agent, enhances insulin release and protects mouse islets. Mol Cell Endocrinol. 2010 Jul 29;323(2):246-55.