GW604714X
(Synonyms: 5-(5-(6-(4-乙酰基哌嗪-1-基)-3-硝基吡啶-2-基)-2-氟亚苄基)噻唑烷-2,4-二酮) 目录号 : GC61599GW604714X是丙酮酸支持的线粒体呼吸(mitochondrialrespiration)的有效选择性抑制剂。GW604714X抑制线粒体丙酮酸载体(MPC)的Ki值<0.1μM。GW604714X也能抑制质膜单羧酸转运蛋白MCT1对L-乳酸的转运,但其浓度要比MPC高4个数量级。
Cas No.:853953-65-8
Sample solution is provided at 25 µL, 10mM.
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GW604714X is a potent and selective inhibitor of mitochondrial respiration supported by pyruvate but not other substrates. GW604714X inhibits the mitochondrial pyruvate carrier (MPC) with a Ki values <0.1 μM. GW604714X also inhibits L-lactate transport by the plasma membrane monocarboxylate transporter MCT1, but at concentrations more than four orders of magnitude greater than the MPC[1].
GW604714X inhibits the mitochondrial pyruvate carrier (MPC) with Ki values <0.1 μM in direct measurement of pyruvate transport into rat liver and yeast mitochondria. 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[1].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[1].
[1]. K K Yamamoto, et al. Isolation of a cDNA encoding a human serum marker for acute pancreatitis. Identification of pancreas-specific protein as pancreatic procarboxypeptidase B. J Biol Chem. 1992 Feb 5;267(4):2575-81.
Cas No. | 853953-65-8 | SDF | |
别名 | 5-(5-(6-(4-乙酰基哌嗪-1-基)-3-硝基吡啶-2-基)-2-氟亚苄基)噻唑烷-2,4-二酮 | ||
Canonical SMILES | O=C(NC/1=O)SC1=C/C2=CC(C3=NC(N4CCN(C(C)=O)CC4)=CC=C3[N+]([O-])=O)=CC=C2F | ||
分子式 | C21H18FN5O5S | 分子量 | 471.46 |
溶解度 | 储存条件 | Store at -20°C | |
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1 mg | 5 mg | 10 mg | |
1 mM | 2.1211 mL | 10.6054 mL | 21.2107 mL |
5 mM | 0.4242 mL | 2.1211 mL | 4.2421 mL |
10 mM | 0.2121 mL | 1.0605 mL | 2.1211 mL |
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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.PMID:15863100DOI:10.1016/j.bbabio.2004.12.005
Two novel thiazolidine compounds, GW604714X and GW450863X, were found to be potent inhibitors of mitochondrial respiration supported by pyruvate but not other substrates. Direct measurement of pyruvate transport into rat liver and yeast mitochondria confirmed that these agents inhibited the mitochondrial pyruvate carrier (MPC) with K(i) values <0.1 muM. Inhibitor titrations of pyruvate-dependent respiration by heart mitochondria gave values (+/-S.E.) for the concentration of inhibitor binding sites (pmol per mg protein) and their K(i) (nM) of 56.0+/-0.9 and 0.057+/-0.010 nM for the more hydrophobic GW604714X; for GW450863X the values were 59.9+/-4.6 and 0.60+/-0.12 nM. [(3)H]-methoxy-GW450863X binding was also used to determine the MPC content of the heart, kidney, liver and brain mitochondria giving values of 56, 40, 26 and 20 pmol per mg protein respectively. Binding to yeast mitochondria was <10% of that in rat liver mitochondria, consistent with the slow rate of pyruvate transport into yeast mitochondria. [(3)H]-methoxy-GW450863X binding was inhibited by GW604714X and by the established MPC inhibitor, UK5099. The absorbance spectra of GW450863X and GW604714X were markedly changed by the addition of beta-mercaptoethanol suggesting that the novel inhibitors, like alpha-cyanocinnamate, possess an activated double bond that attacks a critical cysteine residue on the MPC. However, no labelled protein was detected following SDS-PAGE suggesting that the covalent modification is reversible. GW604714X and GW450863X inhibited l-lactate transport by the plasma membrane monocarboxylate transporter MCT1, but at concentrations more than four orders of magnitude greater than the MPC.