AR-C155858

• CAT Number: I003741
• CAS Number: 496791-37-8
• Molecular Formula: C21H27N5O5S
• Molecular Weight: 461.537
• Purity: ≥95%
• Synonyms: 6-[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-5-[(4S)-4-hydroxy-1,2-oxazolidine-2-carbonyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione
• Target: MCT2
• Solubility: in DMSO > 10 mM
• Storage: Store at -20°C
• IC50: 2.3/<10 nM (Ki, MCT1/2)
• InChI: InChI=1S/C21H27N5O5S/c1-10(2)7-25-20-17(18(28)24(5)21(25)30)16(19(29)26-8-13(27)9-31-26)15(32-20)6-14-11(3)22-23-12(14)4/h10,13,27H,6-9H2,1-5H3,(H,22,23)/t13-/m0/s1
• InChIKey: ISIVOJWVBJIOFM-ZDUSSCGKSA-N
• SMILES: CC1=C(C(=NN1)C)CC2=C(C3=C(S2)N(C(=O)N(C3=O)C)CC(C)C)C(=O)N4CC(CO4)O

AR-C155858(cas 496791-37-8) is a novel inhibitor of the monocarboxylate transporters (MCTs) MCT1 and MCT2 (Ki values are 2.3 and <10 nM respectively); exhibits no activity at MCT4.
Co-expression of exogenous embigin was without effect on either the expression of MCT1 or its inhibition by AR-C155858. In contrast, expression of active MCT2 at the plasma membrane of oocytes was significantly enhanced by co-expression of exogenous embigin. This additional transport activity was insensitive to inhibition by AR-C155858 unlike that by MCT2 expressed with endogenous basigin that was potently inhibited by AR-C155858. Derived values were 2.3+/-1.4 nM, 1.29+/-0.09 nmol per ml of packed cells and 12.2+/-1.1 s-1 respectively. When expressed in Xenopus laevis oocytes, MCT1 and MCT2 were potently inhibited by AR-C155858, whereas MCT4 was not. Inhibition of MCT1 was shown to be time-dependent, and the compound was also active when microinjected, suggesting that AR-C155858 probably enters the cell before binding to an intracellular site on MCT1.

Reference

1:Identification of key binding site residues of MCT1 for AR-C155858 reveals the molecular basis of its isoform selectivity. Nancolas B, Sessions RB, Halestrap AP.Biochem J. 2015 Apr 1;467(1):192. No abstract available. PMID: 25793420
2:Identification of key binding site residues of MCT1 for AR-C155858 reveals the molecular basis of its isoform selectivity. Nancolas B, Sessions RB, Halestrap AP.Biochem J. 2015 Feb 15;466(1):177-88. doi: 10.1042/BJ20141223. Erratum in: Biochem J. 2015 Apr 1;467(1):192. PMID: 25437897 Free PMC Article
3:The inhibition of monocarboxylate transporter 2 (MCT2) by AR-C155858 is modulated by the associated ancillary protein. Ovens MJ, Manoharan C, Wilson MC, Murray CM, Halestrap AP.Biochem J. 2010 Oct 15;431(2):217-25. doi: 10.1042/BJ20100890. PMID: 20695846 Free PMC Article
4:AR-C155858 is a potent inhibitor of monocarboxylate transporters MCT1 and MCT2 that binds to an intracellular site involving transmembrane helices 7-10. Ovens MJ, Davies AJ, Wilson MC, Murray CM, Halestrap AP.Biochem J. 2010 Jan 15;425(3):523-30. doi: 10.1042/BJ20091515. PMID: 19929853 Free PMC Article