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UK-5099

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Chemical Structure| 56396-35-1 同义名 : PF-1005023
CAS号 : 56396-35-1
货号 : A582535
分子式 : C18H12N2O2
纯度 : 98%
分子量 : 288.3
MDL号 : MFCD19443867
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: 50 mg/mL(173.43 mM)，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 mitochondrial pyruvate carriers (MPC) mediate pyruvate import into the mitochondria, which is key to the sustenance of the tricarboxylic cycle and oxidative phosphorylation[3]. In two distinct CRC mouse models, loss of Mpc1 prior to a tumorigenic stimulus doubled the frequency of adenoma formation and produced higher grade tumors. MPC loss was associated with a glycolytic metabolic phenotype and increased expression of stem cell markers. UK-5099 (PF-1005023) is a potent inhibitor of MPC[4]. UK-5099 (PF-1005023) inhibits pyruvate-dependent O2 consumption with an IC50 of 50 nM.[5]. The trypanosomal pyruvate carrier is found to be rather insensitive to inhibition by alpha-cyano-4-hydroxycinnamate (Ki=17 mM) but can be completely blocked by UK-5099 (Ki=49 mM)[6]. UK-5099 also inhibits the monocarboxylate transporter (MCT)[7]. UK5099 significantly inhibits the glucose-stimulated rise in oxygen consumption in a dose-dependent manner and at 150 μM reduced oxygen consumption below basal levels. UK5099 reduces ATP levels and increases ADP and AMP levels in 832/13 cells[8]. The UK5099 treated cells show significantly higher proportion of side population fraction and express higher levels of stemness markers Oct3/4 and Nanog. UK5099 application may be an ideal model for Warburg effect studies[9].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.47mL

0.69mL

0.35mL

17.34mL

3.47mL

1.73mL

34.69mL

6.94mL

3.47mL
参考文献

[1]Zhong Y, Li X, et al. Application of mitochondrial pyruvate carrier blocker UK5099 creates metabolic reprogram and greater stem-like properties in LnCap prostate cancer cells in vitro. Oncotarget. 2015 Nov 10;6(35):37758-69.

[2]Hinoi E, Takarada T, et al. A molecular mechanism of pyruvate protection against cytotoxicity of reactive oxygen species in osteoblasts. Mol Pharmacol. 2006 Sep;70(3):925-35.

[3]Bor Luen Tang. Targeting the Mitochondrial Pyruvate Carrier for Neuroprotection. Brain Sci. 2019 Sep 18;9(9):238.

[4]Claire L Bensard ,et al. Regulation of Tumor Initiation by the Mitochondrial Pyruvate Carrier. Cell Metab. 2020 Feb 4;31(2):284-300.e7.

[5] Halestrap AP. The mitochondrial pyruvate carrier. Kinetics and specificity for substrates and inhibitors. Biochem J. 1975 April; 148(1): 85-96.

[6] Wiemer EA, et al. The inhibition of pyruvate transport across the plasma membrane of the bloodstream form of Trypanosoma brucei and its metabolic implications. Biochem J. 1995 Dec 1;312 ( Pt 2):479-84.

[7]Hinoi E, et al. A molecular mechanism of pyruvate protection against cytotoxicity of reactive oxygen species in osteoblasts. Mol Pharmacol. 2006 Sep;70(3):925-35. Epub 2006 Jun 9.

[8]Patterson JN, et al. Mitochondrial metabolism of pyruvate is essential for regulating glucose-stimulated secretion. J Biol Chem. 2014 May 9;289(19):13335-46.

[9]Zhong Y, et al. Application of mitochondrial pyruvate carrier blocker UK5099 creates metabolic reprogram and greater stem-like properties in LnCap prostate cancer cells in vitro. Oncotarget. 2015 Nov 10;6(35):37758-69.