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- •Proc Natl Acad Sci U S A. 2015 Sep 1;112(35):11090-5.
- •Elife. 2017 Apr 17;6. pii: e24241.
- •J Neurosci. 2015 Mar 11;35(10):4168-78.
- •Oncotarget. 2014 Nov 30;5(22):11029-37.
- •Pharm Res. 2015 Jun;32(6):1894-906.
- •J Cell Physiol. 2017 Jan;232(1):136-44.
- •Am J Physiol Cell Physiol. 2016 Jul 1;311(1):C116-26.
- •PLoS One. 2016 Apr 7;11(4):e0153135.
- •PLoS One. 2014 Jan 21;9(1):e85780.
- •PLoS One. 2013;8(2):e57712.
- •J Pharm Pharmacol. 2014 Apr;66(4):574-83.
| Description |
AR-C155858 is a novel inhibitor of the monocarboxylate transporters (MCTs) MCT1 and MCT2 (Ki values are 2.3 and < 10="" nm,="" respectively),="" and="" exhibits="" no="" activity="" at="" mct4.=""> |
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| IC50 & Target |
Ki: 2.3 nM (MCT1), 10 nM (MCT2) |
| In Vitro |
AR-C155858 (10 nM-100 nM) inhibits MCT1/MCT2 C-terminal chimaeras[1]. AR-C155858 inhibits MCT2, and the 70% inhibition seen at 10 nM is followed by a gradually increasing inhibition which can only be explained by a Ki value of significantly less than 10 nM. AR-C155858 inhibits MCT1 expressed in Xenopus oocytes in a time- and concentration-dependent manner[2]. |
| References |
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| Preparing Stock Solutions |
Please refer to the solubility information to select the appropriate solvent.
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| Kinase Assay
[1] |
MCT kinetic assays are performed by monitoring intracellular pH with H+-sensitive dye BCECF or by determining the uptake of l-[14C]lactate (7.4 MBq/mL). The uptake buffer containes 75 mM NaCl, 2 mM KCl, 0.82 mM MgCl2, 1 mM CaCl2 and 20 mM Tris/Hepes (pH 7.4). AR-C155858 inhibitor titrations are performed at pH 6 with oocytes preincubated for 45 min in a different uptake buffer (75 mM NaCl, 2 mM KCl, 0.82 mM MgCl2, 1 mM CaCl2 and 20 mM Mes, pH 6) containing the required concentration of AR-C155858 prior to measuring the uptake of l-[14C]lactate (0.5 mM). Unless stated otherwise, uptake is determined over 2.5 min for all MCT constructs except for MCT2trn with or without embigin and MCT2/1 with or without embigin, where 5 and 10 min are used respectively. MCE has not independently confirmed the accuracy of these methods. They are for reference only. |
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| Cell Assay
[1] |
AR-C155858 is dissolved in DMSO. The erythrocytes (5% haematocrit) are pre-incubated for 1 h at room temperature (22°C) with or without AR-C155858 at the required concentration before assaying transport of l-lactate (10 mM) at 6°C. Initial rates of transport are calculated by first-order regression analysis of the time course of pH change and converted into nmol of H+/min by determining the pH change induced by small additions of standardized NaOH. MCE has not independently confirmed the accuracy of these methods. They are for reference only. |
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| References |
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| Molecular Weight |
461.53 |
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| Formula |
C₂₁H₂₇N₅O₅S |
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| CAS No. |
496791-37-8 |
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| Storage |
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| Shipping | Room temperature in continental US; may vary elsewhere |
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| Solvent & Solubility |
10 mM in DMSO AR-C155858 is prepared as a 2.5 mg/mL solution in 10% cyclodextrin in normal saline[3]. * "<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation=""> |
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| References |
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Purity: 95.09% ee.: 99.30%
COA (98 KB) HNMR (203 KB) RP-HPLC (158 KB) NP-HPLC (158 KB)
Handling Instructions (1252 KB)-
[1]. Ovens MJ, et al. The inhibition of monocarboxylate transporter 2 (MCT2) by AR-C155858 is modulated by the associated ancillary protein. Biochem J. 2010 Oct 15;431(2):217-25.
[2]. Ovens MJ, et al. AR-C155858 is a potent inhibitor of monocarboxylate transporters MCT1 and MCT2 that binds to an intracellular site involving transmembrane helices 7-10. Biochem J. 2010 Jan 15;425(3):523-30.
[3]. Vijay N, et al. A Novel Monocarboxylate Transporter Inhibitor as a Potential Treatment Strategy for γ-Hydroxybutyric Acid Overdose. Pharm Res. 2015 Jun;32(6):1894-906.
