Key Dates

Related Announcements

PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

PA-20-195 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

PA-20-200 - NIH Small Research Grant Program (Parent R03 Clinical Trial Not Allowed)

PA-20-188 - NIH Pathway to Independence Award (Parent K99/R00 Independent Clinical Trial Not Allowed)

PA-20-190 - Mentored Research Scientist Development Award (Parent K01 - Independent Clinical Trial Not Allowed)

PAR-21-208 - Cutting-Edge Basic Research Awards (CEBRA) (R21 Clinical Trial Optional)

PA-21-049 - Ruth L. Kirschstein National Research Service Award (NRSA) Individual Fellowship for Students at Institutions with NIH-Funded Institutional Predoctoral Dual-Degree Training Programs (Parent F30)

PA-21-050 - Ruth L. Kirschstein National Research Service Award (NRSA) Individual Fellowship for Students at Institutions Without NIH-Funded Institutional Predoctoral Dual-Degree Training Programs (Parent F30)

PA-21-051 - Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship (Parent F31)

PA-21-052 - Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship to Promote Diversity in Health-Related Research (Parent F31-Diversity)

PA-21-048 - Ruth L. Kirschstein National Research Service Award (NRSA) Individual Postdoctoral Fellowship (Parent F32)

Issued by

National Institute on Drug Abuse (NIDA)

Purpose

The purpose of this Notice is to inform potential applicants to the National Institute on Drug Abuse (NIDA) about a special interest in supporting basic research on the application of chemoproteomic approaches for the discovery of targets and for development of drugs to treat addiction and substance use disorders.

Background

Chemoproteomics combines diverse approaches in synthetic chemistry, cell biology and mass spectrometry to covalently modify, identify, and characterize protein targets of interest for drug discovery. Chemical proteomic platforms such as the activity-based protein profiling (ABPP) have proven effective for identifying drug targets in various biological settings. Use of reactivity-based chemical probes and advanced quantitative mass spectrometry-based proteomic techniques have enabled identification of hotspots for ligand binding on proteins including those that are generally considered undruggable. Chemoproteomic methods also enable identification of allosteric binding sites that could be targeted with small molecules to modulate the function of the target proteins. These chemoproteomic approaches, together with emerging technologies such as targeted protein degradation, covalent fragment-based ligand discovery, and biorthogonal chemistry, are transforming the landscape of drug discovery. Development of novel chemoproteomic methods and their application, therefore, holds considerable potential for identifying and illuminating targets of relevance to substance use and for providing leads for the development of drugs for treating substance use disorders.

Research Objectives

The goal of this announcement is to encourage preclinical research aimed at developing and applying chemoproteomic approaches to identify targets of relevance to substance use disorders and to develop novel pharmacological tools, methods, and therapeutic interventions for the treatment of substance use disorders and addiction. Examples of research areas of interest include, but are not limited to:

• Development of chemoproteomic and chemical biology methods to identify novel targets of relevance to substance use disorders
• Application of chemoproteomic techniques to identify potential ligand binding sites on biological targets of relevance to substance use disorders
• Discovery of lead compounds for modulating the function of biological targets of interest by target-based or cell-based screening of covalent ligands
• Application of biophysical methods such as cryo-EM, X-ray, NMR, etc., to gain structural insights into covalent ligand binding and ligand-target interactions
• Application of structure-based drug design and medicinal chemistry approaches to optimize the lead compounds for potency, efficacy, and physicochemical and pharmacokinetic properties
• Use of virtual screening, artificial intelligence, machine learning and computational approaches to aid in covalent ligand discovery and lead optimization
• Application of rational design approaches to generate fluorescent probes and imaging tools to aid in visualizing and understanding spatiotemporal aspects of target distribution and target engagement
• Pharmacological studies using tool compounds to gain mechanistic insights and to establish efficacy, safety, and tolerability

Application and Submission Information

This notice applies to due dates on or after February 5, 2023 and subsequent receipt dates through January 8, 2026.

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcements through the expiration date of this notice.

• PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
• PA-20-195 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)
• PA-20-200 - NIH Small Research Grant Program (Parent R03 Clinical Trial Not Allowed)
• PA-20-188 - NIH Pathway to Independence Award (Parent K99/R00 Independent Clinical Trial Not Allowed)
• PA-20-190 - Mentored Research Scientist Development Award (Parent K01 - Independent Clinical Trial Not Allowed)
• PAR-21-208 - Cutting-Edge Basic Research Awards (CEBRA) (R21 Clinical Trial Optional)
• PA-21-049 - Ruth L. Kirschstein National Research Service Award (NRSA) Individual Fellowship for Students at Institutions with NIH-Funded Institutional Predoctoral Dual-Degree Training Programs (Parent F30)
• PA-21-050 - Ruth L. Kirschstein National Research Service Award (NRSA) Individual Fellowship for Students at Institutions Without NIH-Funded Institutional Predoctoral Dual-Degree Training Programs (Parent F30)
• PA-21-051 - Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship (Parent F31)
• PA-21-052 - Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship to Promote Diversity in Health-Related Research (Parent F31-Diversity)
• PA-21-048 - Ruth L. Kirschstein National Research Service Award (NRSA) Individual Postdoctoral Fellowship (Parent F32)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include NOT-DA-24-005 (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.

Inquiries

Scientific/Research Contact(s)

Sam Ananthan, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-435-2199
Email: sam.ananthan@nih.gov