同义名 :	-
	CAS号 :	1371569-69-5
	货号 :	A927667
	分子式 :	C20H17F3N2O2S
	纯度 :	97%
	分子量 :	406.42
	MDL号 :	MFCD23143626
	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

The glucagon-like peptide-1 receptor (GLP-1R) is one of the preeminent class B G-protein coupled receptor(GPCRs) as both its physiologic control of insulin secretion, and its ligand binding-receptor interactions using structural biology[1]. BETP represents a novel small-molecule activator of GLP-1R, and exhibits glucose-dependent insulin secretion in rats following i.v. (but not oral) administration[2]. Sustained degradation of BETP with small-molecule BET proteolysis-targeting chimera (PROTAC), ARV-825, resulted in marked downregulation of surface CXCR4 and CD44, key proteins in leukemia-microenvironment interaction, in AML cells. BETP degradation markedly decreased CD34+CD38-CD90-CD45RA+ leukemic stem cell population and alone or in combination with Cytarabine, prolonged survival in mouse model of human leukemia including AML-PDX[3]. BETP increases the potency of oxyntomodulin by 10-fold (EC50 of 80 pM). GLP-1 does not change the potencies and efficacies of both oxyntomodulin and glucagon at the glucagon receptor. BETP (0-30 μM) increases the binding affinity of oxyntomodulin for the GLP-1 receptor. BETP (5 mg/kg) enhances oxyntomodulin-stimulated insulin secretion[4]. BETP has insulinotropic effect in SD rats. BETP (10 mg/kg, jugular vein cannula) exhibits insulin secretagogue activity in the intravenous glucose tolerance test (IVGTT) model. BETP (10 mg/kg, i.v.)-treated rats need 20% higher glucose infusion rates and demonstrates higher plasma insulin levels in SD rat hyperglycemic clamp model[5].

实验方案
	1mg	5mg	10mg
1 mM 5 mM 10 mM	2.46mL 0.49mL 0.25mL	12.30mL 2.46mL 1.23mL	24.61mL 4.92mL 2.46mL

参考文献

[1] Jazayeri, A., Rappas, M., Brown, A. J. H., Kean, J., Errey, J. C., Robertson, N. J., et al.(2017). Crystal structure of the GLP-1 receptor bound to a peptide agonist. Nature,546(7657), 254–258. [2]Heather Eng,et al. Demonstration of the innate electrophilicity of 4-(3-(benzyloxy)phenyl)-2-(ethylsulfinyl)-6-(trifluoromethyl)pyrimidine (BETP), a small-molecule positive allosteric modulator of the glucagon-like peptide-1 receptor. Drug Metab Dispos. 2013 Aug;41(8):1470-9. [3]Sujan Piya,et al. BETP degradation simultaneously targets acute myelogenous leukemia stem cells and the microenvironment. J Clin Invest. 2019 Feb 21;129(5):1878-1894. [4]Willard FS, et al. Small molecule allosteric modulation of the glucagon-like Peptide-1 receptor enhances the insulinotropic effect of oxyntomodulin. Mol Pharmacol. 2012 Dec;82(6):1066-73. [5]Sloop KW, et al. Novel small molecule glucagon-like peptide-1 receptor agonist stimulates insulin secretion in rodents and from human islets. Diabetes. 2010 Dec;59(12):3099-107.