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
  • 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.