# Structural and Chemical Analysis of Highly Potent ALLINI Platform

> **NIH NIH R01** · EMORY UNIVERSITY · 2021 · $389,750

## Abstract

Project Summary – Kim
While current anti-HIV therapeutic agents contribute to the effective suppression of HIV-1 in patients, actual
choices for long-term treatment is rather limited due to viral escape, cross-resistance, and toxicity, demanding
discovery of newer and safer classes of anti-HIV agents.
 HIV-1 requires various host intracellular factors for completing its life cycle and pathogenesis. Targeting
the interactions between viral proteins and these host intracellular factors has been extensively explored as a
potential anti-viral discovery path while anti-HIV agents targeting the viral interactions with intracellular factors
are currently limited. A recent collaborative work between Emory Center for Drug Discovery (CDD) and ST
Pharm, CO, LTD identified a highly potent anti-HIV compound with outstanding in vitro and animal toxicity and
pharmacokinetics, STP03-0404: STP03-0404 was originally identified as an anti-HIV hit by the random anti-
HIV compound screening operation of ST Pharm that employed a series of chemical scaffold libraries uniquely
developed by ST Pharm. The EC50 values of STP03-0404 determined by Southern Research Institute (SRI,
Frederick, MD) with human PBMCs and various clinical HIV-1 isolates, and also independently determined by
Emory CDD are in pico-molar ranges. Furthermore, the tissue culture based therapeutic index of STP03-0404
was 40,000-1,000,000, and the preclinical animal investigations with rats and dogs demonstrated its
outstanding safety and excellent pharmacokinetics.
 Excitingly, our extensive computational structure-based search efforts and initial X-ray crystallographic
analysis proposed that STP03-0404 targets the LEDGF/p75 binding pocket at the interface between two
monomers of HIV-1 integrase (IN) and therefore this compound works as an allosteric integrase inhibitor
(ALLINI). Importantly, we found that STP03-0404 displays up to ~ 1,000 times more effective anti-HIV-1 activity
than previously reported ALLINIs. Furthermore, STP03-0404 effectively inhibits clinical HIV-1 strains with
resistance to catalytic site integrase inhibitors such as Raltegravir. Therefore, in this application, we will
structurally and chemically investigate STP03-0404 as a highly potent and safe ALLINI platform. For
these investigations, we propose to employ a series of in-depth biochemical, structural biology,
virological/genetic approaches as well as medicinal chemistry/chemical optimization designed for new
derivatives of STP03-0404 with enhanced genetic barrier to resistance. Ultimate goal of this application is
to meet the current demand for newer and safer anti-HIV agents by pre-clinically investigating STP03-0404 as
a novel, potent and safe anti-HIV drug discovery platform.

## Key facts

- **NIH application ID:** 10239022
- **Project number:** 5R01AI141327-04
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Baek Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $389,750
- **Award type:** 5
- **Project period:** 2018-09-24 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10239022

## Citation

> US National Institutes of Health, RePORTER application 10239022, Structural and Chemical Analysis of Highly Potent ALLINI Platform (5R01AI141327-04). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10239022. Licensed CC0.

---

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