# MECHANISMS OF CYCLOPHOSPHAMIDE ACTIVATION

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 1992 · $180,029

## Abstract

The long-term objective of this research program is to develop novel
types of phosphoramidate antitumor agents directed against specific
cellular targets. Chemical mechanistic information discovered in earlier
years of this project will be utilized to guide the design, synthesis,
and evaluation of these new mechanism-based phosphoramidates. Specific
aims include: 1) Design and synthesis of phosphoramidate analogs that
undergo bioreductive activation and thus are targeted to hypoxic tumor
cells; 2) Design and synthesis of nucleoside phosphoramidate analogs
that can function as prodrugs for nucleotide delivery or as irreversible
enzyme inhibitors; 3) Design and synthesis of phosphoramidate analogs
targeted to specific DNA sequences; 4) Evaluation of new agents both in
vitro and in vivo against established tumor cell lines. Experiments to
date have demonstrated that cytotoxic compounds can be prepared in each
of these series, and that the compounds are synthetically accessible via
techniques currently in use in the laboratory. Antitumor evaluation will
rely primarily on the murine B16 system using a clonogenic assay in
vitro and using regrowth delay and lung metastases in vivo. Other model
systems will be used as needed to assess specific mechanistic
objectives. The ultimate goal is to exploit the unique properties of the
phosphoramidate alkylating moiety to develop new drugs with reduced host
toxicity and/or increases efficacy against resistant or poorly
responsive tumors.

## Key facts

- **NIH application ID:** 3172360
- **Project number:** 2R01CA034619-11
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **SAM.gov UEI:** F27KDXZMF9Y8
- **Principal Investigator:** RICHARD F. BORCH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $180,029
- **Award type:** 2
- **Project period:** 1992-06-01 → 1996-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172360

## Citation

> US National Institutes of Health, RePORTER application 3172360, MECHANISMS OF CYCLOPHOSPHAMIDE ACTIVATION (2R01CA034619-11). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3172360. Licensed CC0.

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