# METABOLIC LIMITATIONS TO THE EFFICACY OF 5FU

> **NIH NIH R01** · CHILDREN'S HOSPITAL OF LOS ANGELES · 1987 · $108,924

## Abstract

The fluoropyrimidines are potent inhibitors of the growth of human and
murine tumor cells in culture and of a spectrum of mouse tumors in vivo but
have limited activity against human tumors in clinical circumstances.
Previous studies have suggested that the activity of these compounds as
inhibitors of thymidylate synthase (and, hence, of DNA synthesis) is
limited in human tumors by rapid accumulation of deoxyuridylate and by the
low availability of folate cofactors.  This research program would study
the factors that limit and control tumor cell death with fluoropyrimidines
and other inhibitors of thymidylate synthase and determine how these
factors differed in mouse and human cells.  Inhibition of thymidylate
synthase would be studied and related to deoxyuridylate accumulation and
5,10-methylenetetrahydrofolate pools.  The rate of cell kill would be
composed in mouse and human cells at sustained equivalent inhibition of
thymidylate synthesis using fluoropyrimidine exposure of wild type cells
and thymine deprivation of genetic mutants lacking enzyme.  The
chemotherapeutic activity of combination of fluoropyrimidine with folinic
acid, with inhibitors of deoxyuridylate synthesis and with new inhibitors
of folate metabolism will be studied using cells in culture and murine
tumors in vivo.  These studies seek to understand why the activity of the
flyoropyrimidines to mouse and human tumors differ and whether the
selective cytotoxicity of the fluoropyrimidines can be extended by
combination with other agents.

## Key facts

- **NIH application ID:** 3173558
- **Project number:** 5R01CA036054-05
- **Recipient organization:** CHILDREN'S HOSPITAL OF LOS ANGELES
- **SAM.gov UEI:** DVL1CMRMWRN9
- **Principal Investigator:** RICHARD G MORAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $108,924
- **Award type:** 5
- **Project period:** 1983-07-01 → 1989-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173558

## Citation

> US National Institutes of Health, RePORTER application 3173558, METABOLIC LIMITATIONS TO THE EFFICACY OF 5FU (5R01CA036054-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173558. Licensed CC0.

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