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AR-C155858

Names

[ CAS No. ]:
496791-37-8

[ Name ]:
AR-C155858

[Synonym ]:
6-[(3,5-Dimethyl-1H-pyrazol-4-yl)methyl]-5-{[(4S)-4-hydroxy-1,2-oxazolidin-2-yl]carbonyl}-1-isobutyl-3-methylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione
6-[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-5-{[(4S)-4-hydroxy-1,2-oxazolidin-2-yl]carbonyl}-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione
Thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, 6-[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-5-[[(4S)-4-hydroxy-2-isoxazolidinyl]carbonyl]-3-methyl-1-(2-methylpropyl)-
Thienopyrimidine-2,4-dione,13
CS-0540
AR-C155858

Biological Activity

[Description]:

AR-C155858 is a selective monocarboxylate transporter MCT1 and MCT2 inhibitor with Kis of 2.3 nM and 10 nM, respectively.

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> Monocarboxylate Transporter
Research Areas >> Others

[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].

[Kinase Assay]

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.

[Cell Assay]

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.

[References]

[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.


[Related Small Molecules]

AZD3965 | UK-5099 | 7-Diethylaminocoumarin-3-carboxylic acid | 7ACC2

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
763.1±70.0 °C at 760 mmHg

[ Molecular Formula ]:
C21H27N5O5S

[ Molecular Weight ]:
461.535

[ Flash Point ]:
415.3±35.7 °C

[ Exact Mass ]:
461.173279

[ PSA ]:
150.69000

[ LogP ]:
0.93

[ Vapour Pressure ]:
0.0±2.7 mmHg at 25°C

[ Index of Refraction ]:
1.634

[ Storage condition ]:
2-8℃

Related Compounds