2. Academic Validation
  3. Exploiting the co-reliance of tumours upon transport of amino acids and lactate: Gln and Tyr conjugates of MCT1 inhibitors

Exploiting the co-reliance of tumours upon transport of amino acids and lactate: Gln and Tyr conjugates of MCT1 inhibitors

  • Medchemcomm. 2016 May 1;7(5):900-905. doi: 10.1039/C5MD00579E.
Reji N Nair 1,  Jitendra K Mishra 1,  Fangzheng Li 1,  Mariola Tortosa 1,  Chunying Yang 2,  Joanne R Doherty 3,  Michael Cameron 4,  John L Cleveland 2,  William R Roush 1,  Thomas D Bannister 1
Affiliations

Affiliations

  • 1 Department of Chemistry, The Scripps Research Institute, 110 Scripps Way, Jupiter, FL 33458, USA.
  • 2 Department of Tumor Biology, Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.
  • 3 Department of Cancer Biology, The Scripps Research Institute, 110 Scripps Way, Jupiter, FL 33458, USA.
  • 4 Department of Molecular Therapeutics, The Scripps Research Institute, 110 Scripps Way, Jupiter, FL 33458, USA.
PMID: 27347360 DOI: 10.1039/C5MD00579E
Abstract

Glutamine and tyrosine-based amino acid conjugates of Monocarboxylate Transporter types 1 and 2 inhibitors (MCT1/2) were designed, synthesized and evaluated for their potency in blocking the proliferation of a human B lymphoma cell line that expresses the transporters ASCT2, LAT1 and MCT1. Appropriate placement of an amino acid transporter recognition element was shown to augment anti-tumour efficacy vs. Raji cells. Amino acid conjugation also improves the pharmacodynamic properties of experimental MCT1/2 inhibitors.

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