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UK-5099 (PF1005023) is a novel potent and specific/selective inhibitor of the mitochondrial pyruvate carrier (MPC), it acts by inhibiting pyruvate transport across the plasma membrane of trypanosomes (Ki = 49 μM). UK-5099 also inhibits pyruvate-dependent O2 consumption (IC50 = 50 nM).
ln Vitro |
The inhibitory impact of alpha-cyano-4-hydroxycinnamate (Ki=17 mM) was found to be somewhat insensitive to the trypanopyruvate carrier; nevertheless, UK-5099 (Ki=49 microM) was able to inhibit it [2]. The monocarboxylate transporter (MCT) is likewise inhibited by UK-5099 [3]. At 150 μM, UK5099 decreased oxygen consumption below basal levels and in a dose-dependent manner prevented the glucose-stimulated increase in oxygen consumption. In 832/13 cells, UK5099 lowers ATP levels while raising ADP and AMP levels [4]. The cells treated with UK5099 exhibited a notably increased fraction of side population and expressed larger amounts of the stemness markers Oct3/4 and Nanog. Warburg effect studies should benefit greatly from using the UK5099 application as a paradigm [5].
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ln Vivo |
In the intraperitoneal glucose tolerance test conducted on C57BLK mice, the MPC inhibitor UK5099 causes an increase in the glucose excursion [4].
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Animal Protocol |
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References |
[1]. Halestrap AP. The mitochondrial pyruvate carrier. Kinetics and specificity for substrates and inhibitors. Biochem J. 1975 April; 148(1): 85-96.
[2]. 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. [3]. 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. [4]. 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. [5]. 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 |
Molecular Formula |
C18H12N2O2
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Molecular Weight |
288.30
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CAS # |
56396-35-1
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SMILES |
O=C(O)/C(C#N)=C/C1=CN(C2=CC=CC=C2)C3=C1C=CC=C3
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Chemical Name |
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Synonyms |
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 3.4686 mL | 17.3430 mL | 34.6861 mL | |
5 mM | 0.6937 mL | 3.4686 mL | 6.9372 mL | |
10 mM | 0.3469 mL | 1.7343 mL | 3.4686 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
UK5099 blocked pyruvate transportation into mitochondrial in LnCap cellsin vitro. Cells treated with UK5099 tended to be highly resistant to cisplatin. th> |
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UK5099 inhibited cell proliferation and changed cell cycle.Oncotarget.2015 Nov 10;6(35):37758-69. td> |
UK5099 attenuated mitochondrial function and increased glycolysis.Oncotarget.2015 Nov 10;6(35):37758-69. td> |
UK5099 increased side population cells and stemness markers in LnCap cell.Oncotarget.2015 Nov 10;6(35):37758-69. th> |
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Metabolic Reprogramming Resulting from Pharmacological Mpc Inhibition Is Distinct from Hypoxia or Complex I Inhibition. Mpc Controls Oxidative Substrate Utilization in Myotubes.Molecular cell. 2014, 56(3):425-4 td> |
An MPC inhibitor suppresses cancer cell growth.Molecular cell. 2014, 56(3):425-4 td> |