# Preclinical Testing of Potential Next-generation Antischistosomal Compounds

> **NIH NIH R56** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2024 · $810,158

## Abstract

PROJECT SUMMARY / ABSTRACT
Human schistosomiasis is a disease caused by species of the genus Schistosoma,
which globally affects over 200 million people. The major species affecting humans are:
S. mansoni, S. haematobium, and S. japonicum. There is currently only one method of
treatment (monotherapy), the drug Praziquantel (PZQ). Constant selection pressure
through mass chemotherapy – this year alone will see the administration of over 250
million doses – has yielded evidence of resistance to PZQ. This has been observed in
both the laboratory and field. The goal of this research is to develop a second drug with
a different mode of action for use in conjunction with PZQ to improve the efficacy of
treatment and mitigate resistance. Previous treatment of S. mansoni included, among
others, the use of oxamniquine (OXA), a prodrug that is taken up by the schistosome
and enzymatically activated within S.mansoni but is ineffective against S. haematobium
and S. japonicum. The OXA activating enzyme was identified as a sulfotransferase
(SmSULT). The focus of this research was to reengineer OXA to be more effective
against S. mansoni and effective against S. haematobium and S. japonicum. We
employed an iterative process in which structural data is used to inform compound
design and chemical synthesis of derivatives, which are then tested in an in vitro killing
assay. The compounds that are best killers are soaked into new crystals and the
process repeated. Over 350 OXA derivatives have been synthesized including CIDD-
0150303 that will kill 100% S. mansoni, S. haematobium and S. japonicum in an in vitro
assay. This derivative also will kill a significant number of schistosomes in an in vivo
model of schistosomiasis. We propose to optimize the leading/top derivative to improve
solubility, bioavailability, prolong it’s action and perform safety and toxicity studies.
These studies will also include determining the physical chemical properties of the
derivative and improvement of desirable drug properties. An additional major focus will
be on the impact of combination therapy with PZQ. The outcome of the proposed
studies will be a novel drug that in combination with PZQ will have a significant impact
on global human health and will lead to improved treatments for Schistosoma to reduce
the morbidity, morality, and transmission rates associated with schistosomiasis. The
Major deliverable will be an OXA derivative that results in a new anthelmintic
candidate ready for formulation, scale-up, and clinical studies.

## Key facts

- **NIH application ID:** 11131505
- **Project number:** 1R56AI180213-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Sevan Najm Alwan
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $810,158
- **Award type:** 1
- **Project period:** 2024-08-19 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11131505

## Citation

> US National Institutes of Health, RePORTER application 11131505, Preclinical Testing of Potential Next-generation Antischistosomal Compounds (1R56AI180213-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11131505. Licensed CC0.

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