# Core A - Discovery Core

> **NIH NIH P01** · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2022 · $294,559

## Abstract

Project Summary
 The screening core will build on our success utilizing conventional and virtual screening approaches to
identify small molecules that regulate bronchomotor tone. The integration of conventional and virtual screening
workflows enabled us to move rapidly from primary screening hits to detailed structure-activity relationships
(SAR), and from computational predictions to quantitative experimental data. The relationships that the core
has established with other regional screening resources (Lankenau Chemical Genomics Center (LCGC);
Natural Products Discovery Institute (NPDI); Monell Chemical Senses Center (MCSC)) ensures access to
high-quality molecular diversity for proposed screening projects, and our validated expertise in second
messenger and protein interaction assays will expedite discovery of probes and targets that bias signaling
pathways in airway smooth muscle using arrayed and expressed sources of molecular diversity.
 The Jefferson Discovery Core provides the conventional screening capabilities for Core A, using in-
house sources of molecular diversity as well as libraries obtained from regional and national resources (NCI-
DTP) to identify small molecules engendering phenotypes that correlate with airway relaxation in cell-based,
high-throughput screening (HTS) assays. Second messenger (cAMP, Ca2+) and protein interaction assays
(enzyme-fragment complementation) have been optimized for detection both in multiwell plates and by
fluorescence-activated cell sorting, which enables use of both arrayed and expressed sources of molecular
diversity for identification of probes and targets regulating signaling pathways affecting bronchomotor tone.
HTS for inhibitors of G12 signaling (project 1), internalization of TAS2R14 (project 2), HTS, SAR and medicinal
chemistry to discover and optimize Gs-biased agonists and allosteric modulators of 2AR (project 3) and
evaluation of Gs-biased allosteric modulators of OGR1 predicted by virtual screening (project 4) are the top
priorities.
 Computational modeling and docking approaches are used by Core A both to direct and inform
conventional screening approaches. CHARMM-based molecular docking approaches will be used to predict
the binding modes of small-molecules identified from high-throughput screening, develop SAR models and
predict derivatives with improved activity and physiochemical properties. These studies are synergistic with
parallel experimental HTS efforts, particularly in following-up on the most promising hits identified from HTS.
Parallel modeling studies of small-molecule allosteric modulators of 2AR and OGR1 will be aimed at
identifying common structural features leading to Gs-biased signaling. Structure-based knowledge will be used
to inform parallel virtual screening strategies to identify novel allosteric modulators of 2AR and OGR1. Finally,
a virtual screening approach will be used to identify small-molecule inhibitors of G12 and Gq that would mimic
the pharmacologi...

## Key facts

- **NIH application ID:** 10465059
- **Project number:** 7P01HL114471-09
- **Recipient organization:** RUTGERS BIOMEDICAL AND HEALTH SCIENCES
- **Principal Investigator:** Jeffrey L Benovic
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $294,559
- **Award type:** 7
- **Project period:** 2013-07-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465059

## Citation

> US National Institutes of Health, RePORTER application 10465059, Core A - Discovery Core (7P01HL114471-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10465059. Licensed CC0.

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