# MECHANISMS OF CYLCOPHOSPHAMIDE ACTIVATION

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 1987 · $185,091

## Abstract

Cyclophasphamide is the most widely used agent in the
treatment of numerous hematologic and solid human tumors.
The long-term objective of this research is to develop new types
of cyclophosphamide-based antitumor agents and study their
mechanisms of activation, action, and toxicity.  The approach
will be based upon the specific chemical mechanistic information
discovered during the previous grant period.  This information
will be utilized to guide the design, synthesis, and evaluation of
new mechanism-based phosphoramidate antitumor agents.
Specific aims include 1) Determination of the cytotoxic
contribution of intracellular vs. extracellular release of the
alkylating agent phosphoramide mustard; 2) Continuation of the
synthesis, development, and cytotoxic evaluation of substituted
aldophosphamide analogs designed for activity against
cyclophosphamide-resistant cells; 3) Development of a new
series of cyclophosphamide analogs designed as bioreductive
alkylating agents to achieve cytotoxic specificity against
hypoxic cells; 4) Development of a series of aldophosphamide
analogs designed to deliver cytotoxic nucleotides and analogs to
tumor cells.  Nuclear magnetic resonance (NMR) will be the
primary technique used to measure drug activation and
breakdown in vitro, and this data will be used in the design of
new analogs.  All new compounds will initially be evaluated in
cell culture against established murine tumor lines, and
compounds showing activity will also be tested in vivo.  Our goal
is to utilize the unique activation pathways of cyclophosphamide
to develop new drugs with reduced host toxicity and/or increased
efficacy against resistant or poorly responsive tumor cells.

## Key facts

- **NIH application ID:** 3172359
- **Project number:** 2R01CA034619-06
- **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:** 1987
- **Award amount:** $185,091
- **Award type:** 2
- **Project period:** 1982-09-01 → 1992-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172359

## Citation

> US National Institutes of Health, RePORTER application 3172359, MECHANISMS OF CYLCOPHOSPHAMIDE ACTIVATION (2R01CA034619-06). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3172359. Licensed CC0.

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