# Novel Therapeutics to Target Parasite Cytochrome bc1

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $620,090

## Abstract

Project Summary / Abstract
The Medicines for Malaria Venture (MMV) recently published a “roadmap” for the types of medicines that are
needed to support the long-term goal of malaria elimination and eradication. The roadmap consists of a wish list
of target candidate profiles (TCP) and medicines (target product profiles, i.e., TPP). With the most recent revision
to the anti-malarial target candidates and product profiles the MMV highlighted the need for identifying new rapid
acting medicines for active case management while other drugs are needed for chemo-protection and chemo-
prevention with long-acting molecules, and/or parenteral formulations (i.e., TCP-2) (Burrows, JN et al., 2017,
Malaria Journal, 16:26). According to their updated roadmap new drugs are needed to protect populations
entering areas of high endemicity during the final stages of malaria elimination. And drugs with causal liver-
stage activity are needed for chemoprevention to prevent infection or outbreak of resistance during malarial
seasons. This TCP has been modeled on the combination drug atovaquone + proguanil.
As a potent and selective inhibitor of the parasite’s cytochrome bc1 complex ELQ-300 selectively targets
Plasmodium falciparum in the blood and liver stages and even kills parasites developing in the midgut of the
mosquito vector. Unlike atovaquone, ELQ-300 is a selective inhibitor of the Qi site of the target enzyme complex.
With support from the NIH and US DOD we have been successful in developing an oral formulation of prodrug
ELQ-331 for use in humans for weekly prophylaxis against malaria. In the present application we seek NIH
support for work to develop ELQ derivatives that more effectively and comprehensively inhibit the parasite
cytochrome bc1 complex. Advanced designs for improved ELQ constructs are supported by preliminary data
provided with the application as well as our extensive knowledge of Endochin-Like Quinolone derivatives as
inhibitors of the Plasmodium falciparum cytochrome bc1 Qo or Qi sites. Superior molecules will advance through
a down-selection test cascade for assessment of selective potency and lack of mammalian cytotoxicity,
metabolic stability, solubility in simulated intestinal fluids, resistance propensity and mode of action as well as
efficacy against blood and liver stage malaria in mice. Prodrugs of superior molecules will be explored to assess
for enhancement of oral bioavailability and antimalarial performance over parent molecules.

## Key facts

- **NIH application ID:** 10870040
- **Project number:** 5R01AI100569-11
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Michael Kevin RISCOE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $620,090
- **Award type:** 5
- **Project period:** 2012-07-15 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10870040

## Citation

> US National Institutes of Health, RePORTER application 10870040, Novel Therapeutics to Target Parasite Cytochrome bc1 (5R01AI100569-11). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10870040. Licensed CC0.

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