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MB05032

现货
Catalog No.
A3586
GNG抑制剂
组合的产品项目
规格价格库存 数量
2mg
¥ 1,680.00
现货
5mg
¥ 2,640.00
Ship with 10-15 days
10mg
¥ 3,960.00
Ship with 10-15 days
50mg
¥ 10,560.00
Ship with 10-15 days
100mg
¥ 18,970.00
Ship with 10-15 days

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Background

MB05032 is a potent and selective GNG inhibitor targeted the AMP binding site of fructose 1,6-bisphosphatase (FBPase) with an IC50 value of 16 nM [1].Gluconeogenesis (GNG) is a metabolic pathway which could result in the generation of glucose from certain non-carbohydratecarbon substrates.

In vitro: MB06322 inhibited glucose synthesis by human hepatocytes over a narrow concentration range with full inhibition achieved at 1 μM in a concentration-dependent manner [2]. MB05032 inhibited human liver FBPase with a potency (IC50 of 16 ± 1.5 nM) significantly greater than the natural inhibitor, AMP (IC50 of 1 μM), and the most well characterized AMP mimetic, ZMP (IC50of 12 ± 1.4 μM). MB05032 inhibited rat FBPase 3-fold weaker (IC50 of 61 ± 4 nM) than human FBPase, whereas AMP was 20-fold weaker as an inhibitor [1]. In islet β-cells,inhibition of FBPase activity by MB05032 led to a significant increase of their glucose utilization and cellular ATP to ADP ratios and consequently enhanced GSIS in vitro [2].

In vivo: In male ZDF rats, oral administration of MB06322 resulted in dose-dependent inhibition of [14C]bicarbonate incorporation into glucose. Maximal GNG inhibition (≈80%) is achieved at 100–300 mg/kg MB06322. In MB06322-treated rats, intermediates upstream of FBPase WERE elevated 1.5- to 3.1-fold relative to vehicle-treated mice. MB06322 treatment also resulted in elevated lactate levels (79%) only in aged ZDF rats. [2]. Oral administration of MB06322 to young (8–9 weeks old) ZDF rats with mild diabetes (basal insulin levels of 7.7 ± 0.7 ng/ml) and aged (12–13 weeks) ZDF rats with overt diabetes (basal insulin levels of 0.65 ± 0.16 ng/ml) lowered the level of glucose in a dose-dependent manner [1]. The dose–dependent response is relatively steep, with 6–10 mg/kg and 30–100 mg/kg being the approximate doses associated with minimal and maximal activity, respectively. After drug administration 2.5–5 h, glucose lowering occurs rapidly with maximal effects [1].

References:
[1] Erion M D, van Poelje P D, Dang Q, et al.  MB06322 (CS-917): A potent and selective inhibitor of fructose 1, 6-bisphosphatase for controlling gluconeogenesis in type 2 diabetes[J]. Proceedings of the National Academy of Sciences, 2005, 102(22): 7970-7975.
[2] Zhang Y, Xie Z, Zhou G, et al.  Fructose-1, 6-bisphosphatase regulates glucose-stimulated insulin secretion of mouse pancreatic β-cells[J]. Endocrinology, 2010, 151(10): 4688-4695.

文献引用

1. Guo B, Huang X, et al. "Antagonism of PPAR-γ signaling expands human hematopoietic stem and progenitor cells by enhancing glycolysis." Nat Med. 2018 Mar;24(3):360-367. PMID:29377004

Chemical Properties

StorageStore at -20°C
M.Wt302.29
Cas No.261365-11-1
FormulaC11H15N2O4PS
SynonymsMB-05032;MB05032
SolubilitySoluble in DMSO
Chemical Name(5-(2-amino-5-isobutylthiazol-4-yl)furan-2-yl)phosphonic acid
SDFDownload SDF
Canonical SMILESNC1=NC(C2=CC=C(P(O)(O)=O)O2)=C(CC(C)C)S1
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验[1]:

结合实验

在将果糖6-磷酸的产生与NADP +的还原相结合的反应中,分光光度法测量果糖1,6-二磷酸酶(FBPase)活性。通过使用肽底物SAMS测定AMP活化蛋白激酶(大鼠肝脏)。将AMP脱氨酶(猪心脏)纯化并如参考文献21中所述测定。如参考文献中所述测定糖原磷酸化酶(兔肌肉),磷酸果糖激酶(兔肝)和腺苷酸激酶(兔肌)。通过使用SIGMAPLOT 2000软件的四参数逻辑回归计算动力学参数。

细胞实验[1]:

细胞系

大鼠和人肝细胞

溶解方法

该化合物可溶于DMSO。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

0.001-100 μM; 15-30 min

应用

在大鼠和人肝细胞中,MB05032浓度依赖性地抑制从所有常见GNG前体产生葡萄糖。与MB06322相比,MB05032对大鼠和人肝细胞合成葡萄糖的抑制分别弱5和226倍。

References:

[1] Erion M D, van Poelje P D, Dang Q, et al. MB06322 (CS-917): A potent and selective inhibitor of fructose 1, 6-bisphosphatase for controlling gluconeogenesis in type 2 diabetes[J]. Proceedings of the National Academy of Sciences, 2005, 102(22): 7970-7975.

质量控制

质量控制和MSDS

批次:

化学结构

MB05032

相关生物数据

MB05032