Abstract

The goal of this project is to characterize the structure and function of the human """"""""classical"""""""" reduced folate carrier (RFC). Human cDNAs isolated in the applicant's laboratory restore MTX sensitivity and RFC activity in transport-defective Chinese hamster ovary cells. Studies are proposed to use anti-RFC antisera to examine structural and functional relationships between other folate transport proteins and the RFC, clone the gene for the RFC and map the intron/exon boundaries and promoter region and identify the structural and functional domains of the human RFC.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA053535-07
Application #
2654068
Study Section
Experimental Therapeutics Subcommittee 1 (ET)
Program Officer
Johnson, George S
Project Start
1993-02-12
Project End
1999-01-31
Budget Start
1998-02-01
Budget End
1999-01-31
Support Year
7
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Wayne State University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202

  Publications

Shah, Khushbu; Raghavan, Sudhir; Hou, Zhanjun et al. (2018) Development and validation of chemical features-based proton-coupled folate transporter/activity and reduced folate carrier/activity models (pharmacophores). J Mol Graph Model 81:125-133
Matherly, Larry H; Hou, Zhanjun; Gangjee, Aleem (2018) The promise and challenges of exploiting the proton-coupled folate transporter for selective therapeutic targeting of cancer. Cancer Chemother Pharmacol 81:1-15
Ravindra, Manasa; Wilson, Mike R; Tong, Nian et al. (2018) Fluorine-Substituted Pyrrolo[2,3- d]Pyrimidine Analogues with Tumor Targeting via Cellular Uptake by Folate Receptor ? and the Proton-Coupled Folate Transporter and Inhibition of de Novo Purine Nucleotide Biosynthesis. J Med Chem 61:4228-4248
Giovannetti, E; Zucali, P A; Assaraf, Y G et al. (2017) Role of proton-coupled folate transporter in pemetrexed resistance of mesothelioma: clinical evidence and new pharmacological tools. Ann Oncol 28:2725-2732
Hou, Zhanjun; Gattoc, Leda; O'Connor, Carrie et al. (2017) Dual Targeting of Epithelial Ovarian Cancer Via Folate Receptor ? and the Proton-Coupled Folate Transporter with 6-Substituted Pyrrolo[2,3-d]pyrimidine Antifolates. Mol Cancer Ther 16:819-830
Wilson, Mike R; Hou, Zhanjun; Yang, Si et al. (2016) Targeting Nonsquamous Nonsmall Cell Lung Cancer via the Proton-Coupled Folate Transporter with 6-Substituted Pyrrolo[2,3-d]Pyrimidine Thienoyl Antifolates. Mol Pharmacol 89:425-34
Golani, Lalit K; Wallace-Povirk, Adrianne; Deis, Siobhan M et al. (2016) Tumor Targeting with Novel 6-Substituted Pyrrolo [2,3-d] Pyrimidine Antifolates with Heteroatom Bridge Substitutions via Cellular Uptake by Folate Receptor ? and the Proton-Coupled Folate Transporter and Inhibition of de Novo Purine Nucleotide Biosynthesi J Med Chem 59:7856-76
Wilson, Mike R; Hou, Zhanjun; Wilson, Lucas J et al. (2016) Functional and mechanistic roles of the human proton-coupled folate transporter transmembrane domain 6-7 linker. Biochem J 473:3545-3562
Wang, Yiqiang; Mitchell-Ryan, Shermaine; Raghavan, Sudhir et al. (2015) Novel 5-substituted pyrrolo[2,3-d]pyrimidines as dual inhibitors of glycinamide ribonucleotide formyltransferase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase and as potential antitumor agents. J Med Chem 58:1479-93
Wang, Lei; Wallace, Adrianne; Raghavan, Sudhir et al. (2015) 6-Substituted Pyrrolo[2,3-d]pyrimidine Thienoyl Regioisomers as Targeted Antifolates for Folate Receptor ? and the Proton-Coupled Folate Transporter in Human Tumors. J Med Chem 58:6938-59

Showing the most recent 10 out of 32 publications