产品说明书

BETP

Print
Chemical Structure| 1371569-69-5 同义名 : -
CAS号 : 1371569-69-5
货号 : A927667
分子式 : C20H17F3N2O2S
纯度 : 97%
分子量 : 406.421
MDL号 : MFCD23143626
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(61.51 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
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.