# A Preclinical Program for Targeting Mycobacterium tuberculosis KasA

> **NIH NIH R01** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2021 · $826,401

## Abstract

ABSTRACT
 We present herein a grant application focused on the late-stage development of
preclinical candidate JSF-3285. Per our recently published research, we have disclosed
the genesis of this program that led to the hit compound DG167 and identification of the
essential β-keto acyl synthase KasA as its target. Building on this effort, our preliminary
data detail the optimization to arrive at JSF-3285 which is efficacious in the acute and
chronic models of M. tuberculosis infection in mice at doses as low as 5 mg/kg once-daily
oral. This proposal seeks to build on this data by conducting the requisite drug
combination and relapse studies to achieve clinical status and begin IND-enabling
studies. In addition, we propose a second generation program based on preliminary data
consisting of a structurally distinct amide series with promising in vitro efficacy, mouse
PK, and X-ray structural data. The grant's second aim will evolve this series, leveraging
our extensive X-ray structural data, SAR, and machine learning models, to produce at
minimum novel early lead compounds if not compounds equal to or surpassing JSF-3285.
The sum total of the two aims, featuring JSF-3285 and second generation candidate/s,
will lend a high probability to a KasA inhibitor becoming clinically relevant in the next 5
years.

## Key facts

- **NIH application ID:** 10209330
- **Project number:** 1R01AI153145-01A1
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** Joel Stephen Freundlich
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $826,401
- **Award type:** 1
- **Project period:** 2021-08-10 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10209330

## Citation

> US National Institutes of Health, RePORTER application 10209330, A Preclinical Program for Targeting Mycobacterium tuberculosis KasA (1R01AI153145-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10209330. Licensed CC0.

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