# A-RING SUBSTITUTED ESTROGENS AS BREAST TUMOR INHIBITORS

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 1988 · $121,314

## Abstract

Certain A-ring substituted estrogens are excellent inhibitors of
hormone dependent breast cancer in 3 different animal models.
Four-substitution on estrone by either nitro- or amine groups
imparts carcinostatic properties to the molecule while diminishing
the estrogenic and toxic properties of this hormone.  It is
proposed in this renewal application; 1) to continue the
investigations of growth inhibition of hormone dependent breast
tumors by A-ring substituted estrogens.  These studies will extend
and refine the present understanding of the effect of A-ring
substitutions on tumor inhibition as well as establish their
influence on the cell cycle with flow cytometric studies; 2) to
carry out formulation and pharmacokinetic studies directed
toward improving the potency of these agents, particularly
following oral administration; 3) to investigate the effects of
combination therapy in rodent models of hormone dependent
breast cancer.  These studies will take advantage of the
apparently separate mechanisms of activity shown by the A-ring
substituted estrogens (4-nitro- and 4-aminoestrone) that are
capable of receptor binding, and the A-ring substituted 3-
deoxyestrogens which inhibit mammary tumors without receptor
involvement.  Furthermore these studies will examine the
efficacy of utilizing the progesterone receptor inductive capacity
of the tumor inhibitory 4-nitroestrone 3-methyl ether in
treatment regimens involving progesterone and the antiprogestin
(RU486).  Combinations with tamoxifen and chemotherapeutic
agents will also be examined; 4) to examine the characteristics,
fate and activity of the estrogen receptor in MXT tumors during
treatment with A-ring substituted estrogens and classical anti-
estrogens.  In every incidence, the A-ring substituted estrogens
are more efficiacious than diethylstilbestrol or tamoxifen when
examined in the rodent tumor systems.  Although effectual,
tamoxifen exhibits some undesirable side effects and this
antiestrogen is, apparently, inactive in certain human tumors that
are otherwise responsive to hormonal treatment.  Thus, new
hormonal agents are needed in the armamentarium to combat
breast cancer:  a) to expand the spectrum of neoplasms that
respond to hormonal therapy and; b) to provide insight into the
characteristics of hormone dependent cancers.

## Key facts

- **NIH application ID:** 3175250
- **Project number:** 2R01CA037387-04A1
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **SAM.gov UEI:** M6K6NTJ2MNE5
- **Principal Investigator:** SAMUEL C BROOKS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $121,314
- **Award type:** 2
- **Project period:** 1984-04-01 → 1991-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175250

## Citation

> US National Institutes of Health, RePORTER application 3175250, A-RING SUBSTITUTED ESTROGENS AS BREAST TUMOR INHIBITORS (2R01CA037387-04A1). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3175250. Licensed CC0.

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