# Systems Approaches for Opening Therapeutic Windows

> **NIH NIH DP2** · YALE UNIVERSITY · 2020 · $2,130,573

## Abstract

Project Summary/Abstract
The overwhelming majority of drugs in development fail. This is a major problem; solutions to this problem
offer potential to benefit humanity by increasing the number of drugs available to treat and help ailing
individuals. Drug companies have a set of tools that enable them to manipulate the biochemical properties of
drugs, but the ultimate success or failure of a drug reflects how the drug affects physiological systems. This
project is based on the idea better drug development strategies that result in wide and favorable therapeutic
windows can be developed through the consideration of systems behaviors. The first major component of this
project investigates the hypothesis that failed drugs can be converted into clinically useful drugs through co-
treatment with another drug that targets the same biological network to “open the therapeutic window”. New
screening approaches will be developed that are optimized to detect therapeutic windows. These screens will
then be applied to high-priority drug targets for which good drugs with favorable therapeutic windows have
largely evaded development. Candidate window openers will be experimentally validated. The second major
component of this project investigates the hypothesis that the mechanisms by which pathogenic variants
promote disease within biological systems can be categorized into recurrent classes of “disease network
motifs”. Additionally, it is hypothesized that analysis of disease network motifs can identify targetable
vulnerabilities that will apply to the different maladies that are promoted through the corresponding disease
network motif. Mathematical and bioinformatic approaches will be used to classify disease network motifs and
to identify their nodes that are likely to have therapeutic windows. Experiments will test the vulnerabilities
identified through this analysis. One set of experiments will focus on existing drugs that can serve as
archetype examples for the disease network motif vulnerabilities. The other set of experiments will utilize the
disease network motif approach to identify new subsets of patients who may be treatable through currently
FDA approved agents. Overall, the proposed research aims to provide a systems perspective to an area of
drug development that needs new strategies to identify the drug targets most likely to result in clinically useful
agent. If successful, this project could make the drug development process more efficient and more
productive, in turn, providing more benefit to more patients more rapidly.

## Key facts

- **NIH application ID:** 10686679
- **Project number:** 7DP2AT011327-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Edward C. Stites
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,130,573
- **Award type:** 7
- **Project period:** 2020-08-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10686679

## Citation

> US National Institutes of Health, RePORTER application 10686679, Systems Approaches for Opening Therapeutic Windows (7DP2AT011327-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10686679. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*