# Molecular and Dynamic Insights into the Function of GPCRs Involved in Drug Abuse

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $550,817

## Abstract

Deaths from drug overdoses have hit record numbers in the US, far exceeding the number of deaths from guns
or car accidents. Sixty percent of these deaths are caused by either illegal drugs (e.g., heroin) or legal
prescription opioids (e.g., Oxycontin and Percocet). Not only has this drawn the attention of the federal
government with specific requests to address the issue by increasing drug tracking, enforcement, and public
awareness, but also doctors have changed the way they treat pain, becoming more hesitant to prescribe
opioids because of the controversy surrounding their abuse. However, effective treatments for pain
management are still lacking for the over 110 million American adults suffering from chronic pain, and a full
resolution of the problem will most likely require a molecular level understanding of how these drugs work so
as to determine how to fine-tune opioid signaling towards the desired therapeutic pathways and away from
those mediating adverse effects. This information is essential to eventually design powerful chemical tools that
may be developed into improved therapeutics.
Building upon the growing body of evidence suggesting that opioid allosteric modulators and G protein-biased
opioid agonists may act as improved painkillers with reduced side effects, the overall goal of the work
described in this application is to obtain atomistic information about alternative (allosteric) binding sites and/or
ligand-specific (biased) conformations of opioid receptors, including details of drug-receptor binding kinetics,
for use as new, exciting avenues to eventually discover improved therapeutics. To this end, we will employ a
computation-driven approach for hypothesis generation of unique mechanistic insights into opioid receptor
function that will be tested iteratively by independently funded investigators. These studies are expected to
significantly impact biomedical research by helping us establish the value of opioid allosteric modulation,
biased agonism, and binding kinetics in drug discovery.

## Key facts

- **NIH application ID:** 10163829
- **Project number:** 5R01DA045473-04
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Marta Filizola
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $550,817
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163829

## Citation

> US National Institutes of Health, RePORTER application 10163829, Molecular and Dynamic Insights into the Function of GPCRs Involved in Drug Abuse (5R01DA045473-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10163829. Licensed CC0.

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