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GW604714X

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Chemical Structure| 853953-65-8 同义名 : -
CAS号 : 853953-65-8
货号 : A1437975
分子式 : C21H18FN5O5S
纯度 : 98%
分子量 : 471.462
MDL号 : MFCD33402205
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMF: 5 mg/mL(10.61 mM)，配合低频超声助溶
动物实验配方：
生物活性
描述 Mitochondrial pyruvate carrier (MPC), composed of MPC1 and MPC2,which is essential for mitochondrial pyruvate usage, mediates the transport of cytosolic pyruvate into mitochondria. Low MPC expression is associated with various cancers, and functionally associated with glycolytic metabolism and stemness[2]. MPC abundance was reduced in failing hypertrophic human hearts, as well as in the myocardium of mice induced to fail by angiotensin II or through transverse aortic constriction. Constitutive knockout of cardiomyocyte MPC1/2 in mice resulted in cardiac hypertrophy and reduced survival, while tamoxifen-induced cardiomyocyte-specific reduction of MPC1/2 to the attenuated levels observed during pressure overload was sufficient to induce hypertrophy with impaired cardiac function[3]. The expression of MPC-1 was decreased in PDA cell lines and tissues, and negatively associated with tumor poorer differentiation, lymph nodes metastasis, higher TNM stages, and patients' overall survival (OS)[4].GW604714X is a potent inhibitor of mitochondrial respiration supported by pyruvate but not other substrates. GW604714X is a highly specific mitochondrial pyruvate carrier (MPC) inhibitor with a Ki <0.1 nM. GW604714X also inhibits L-lactate transport by the plasma membrane monocarboxylate transporter (MCT1), but at concentrations more than 4 orders of magnitude greater than the MPC. Inhibitor titrations of pyruvate-dependent respiration by heart mitochondria gave values for the concentration of inhibitor binding sites and their Ki (nM) of 56.0 nM and 0.057 nM for the GW604714X.GW604714X inhibits the transport of 0.5 mM [14C]-l-lactate into rat red blood cells, mediated by the monocarboxylate transporter MCT1. GW604714X at 10 μM reduces the initial rate of uptake to 30% of control values[5].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.12mL

0.42mL

0.21mL

10.61mL

2.12mL

1.06mL

21.21mL

4.24mL

2.12mL
参考文献

[1]Hildyard JC, Ammälä C, Dukes ID, Thomson SA, Halestrap AP. Identification and characterisation of a new class of highly specific and potent inhibitors of the mitochondrial pyruvate carrier. Biochim Biophys Acta. 2005 Apr-May;1707(2-3):221-30. doi: 10.1016/j.bbabio.2004.12.005. Epub 2004 Dec 30. PMID: 15863100.

[2] Eunjin Koh,et al. MPC1 is essential for PGC-1α-induced mitochondrial respiration and biogenesis. Biochem J. 2018 May 18;475(10):1687-1699.

[3] Mariana Fernandez-Caggiano,et al. Mitochondrial pyruvate carrier abundance mediates pathological cardiac hypertrophy. Nat Metab. 2020 Nov;2(11):1223-1231.

[4] Jiujie Cui,et al. A novel KDM5A/MPC-1 signaling pathway promotes pancreatic cancer progression via redirecting mitochondrial pyruvate metabolism. Oncogene. 2020 Jan;39(5):1140-1151.

[5]John C W Hildyard, et al. Identification and characterisation of a new class of highly specific and potent inhibitors of the mitochondrial pyruvate carrier. Biochim Biophys Acta. Apr-May 2005;1707(2-3):221-30.