title: Exploiting the co-reliance of tumours upon transport of amino acids and lactate: Gln and Tyr conjugates of MCT1 inhibitors.
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.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 110 Scripps Way, Jupiter, FL 33458, USA.
authors.forename: Reji N
authors.initials: RN
authors.lastname: Nair
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 110 Scripps Way, Jupiter, FL 33458, USA.
authors.forename: Jitendra K
authors.initials: JK
authors.lastname: Mishra
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 110 Scripps Way, Jupiter, FL 33458, USA.
authors.forename: Fangzheng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 110 Scripps Way, Jupiter, FL 33458, USA.
authors.forename: Mariola
authors.initials: M
authors.lastname: Tortosa
authors.affiliation: Department of Tumor Biology, Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.
authors.forename: Chunying
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Cancer Biology, The Scripps Research Institute, 110 Scripps Way, Jupiter, FL 33458, USA.
authors.forename: Joanne R
authors.initials: JR
authors.lastname: Doherty
authors.affiliation: Department of Molecular Therapeutics, The Scripps Research Institute, 110 Scripps Way, Jupiter, FL 33458, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Cameron
authors.affiliation: Department of Tumor Biology, Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Cleveland
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 110 Scripps Way, Jupiter, FL 33458, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Roush
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 110 Scripps Way, Jupiter, FL 33458, USA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Bannister