MCT2

Monocarboxylate transporter 2 (MCT2, SLC16A7) is a high-affinity proton-linked transporter mediating cellular uptake of pyruvate and lactate, essential for energy metabolism in neurons, sperm, and renal proximal tubules^[1]^[2]^[3]. Mechanistically, MCT2 requires association with the ancillary glycoprotein embigin for efficient plasma membrane localization and optimal transport activity, distinguishing it from MCT1 which preferentially associates with basigin^[4]^[5]. Extracellular carbonic anhydrase IV further augments MCT2 transport function through non-catalytic proton shuttling, whereas cytosolic carbonic anhydrase II does not affect its activity^[6]. Compared with MCT1 and MCT4, MCT2 exhibits tenfold higher substrate affinity, enabling rapid uptake at low extracellular concentrations, which is critical in tissues with limited substrate availability^[2]^[1]. In disease contexts, MCT2 is widely expressed in cancer cell lines, suggesting pre-translational regulation in neoplastic transformation and potential vulnerability to metabolic inhibition^[1]^[3]. Isoform-specific inhibitors, such as AR-C155858 and Tucatinib, selectively inhibit MCT2 transport when embigin is present, providing tools for mechanistic studies and therapeutic exploration in oncology^[4]^[7]^[5]. These inhibitors bind intracellular transmembrane domains, modulating substrate affinity and enabling precise interrogation of MCT2 function in experimental models^[8]^[7]. Collectively, MCT2’s high affinity, isoform-specific regulation, and responsiveness to pharmacological agents make it a pivotal target for research on metabolic flux and tumor metabolism^[3]^[5].

References:

[1]. Halestrap AP, et al. The monocarboxylate transporter family--role and regulation. IUBMB Life. 2012 Feb;64(2):109-19. [Content Brief]

[2]. Halestrap AP, et al. The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochem J. 1999;343(Pt 2):281-299.

[3]. Halestrap AP, et al. Monocarboxylate transporters (MCTs): structure, roles, regulation and potential as therapeutic targets. Front Pharmacol. 2014;Conference Abstract.

[4]. 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. [Content Brief]

[5]. 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. [Content Brief]

[6]. Klier M, et al. Transport activity of the high-affinity monocarboxylate transporter MCT2 is enhanced by extracellular carbonic anhydrase IV but not by intracellular carbonic anhydrase II. J Biol Chem. 2011 Aug 5;286(31):27781-91. [Content Brief]

[7]. Lin RY, et al. Human monocarboxylate transporter 2 (MCT2) is a high affinity pyruvate transporter. J Biol Chem. 1998 Oct 30;273(44):28959-65. [Content Brief]

[8]. Nancolas B, et al. Identification of key binding site residues of MCT1 for AR-C155858 reveals the molecular basis of its isoform selectivity. Biochem J. 2015 Feb 15;466(1):177-88. [Content Brief]

[9]. Xu B, et al. Structure-guided screening identifies Tucatinib as dual inhibitor for MCT1/2. EMBO Rep. 2026 Feb;27(3):677-703. [Content Brief]

MCT2 Inhibitor (1)

MCT2 Related Products (1):

Cat. No.	Product Name	Effect	Purity

HY-13248

AR-C155858	Inhibitor	99.62%
AR-C155858 is a selective monocarboxylate transporter MCT1 and MCT2 inhibitor with K_is of 2.3 nM and 10 nM, respectively.

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