Evidence map›Paper›PMID 42080628›Full record

ArticleClinical pharmacology and therapeutics2026

Repurposing Drugs for Malaria through a Human Dose Prediction: A Case Study with Berzosertib.

Devasha Redhi, Mwila Mulubwa, Mmakwena M Mmonwa, Mathew Njoroge, Liezl Krugmann, Kelly Chibale

Abstract read
In one paragraph

Article in Clinical pharmacology and therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Devasha RedhiSouth African Medical Research Council Drug Discovery and Development Research Unit, Department of Chemistry and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.ORCID https://orcid.org/0009-0004-9569-8866
Mwila MulubwaHolistic Drug Discovery and Development (H3D) Centre, University of Cape Town, Cape Town, South Africa.ORCID https://orcid.org/0000-0003-2404-9717
Mmakwena M MmonwaHolistic Drug Discovery and Development (H3D) Centre, University of Cape Town, Cape Town, South Africa.ORCID https://orcid.org/0000-0002-6968-4231
Mathew NjorogeHolistic Drug Discovery and Development (H3D) Centre, University of Cape Town, Cape Town, South Africa.ORCID https://orcid.org/0000-0003-1276-2224
Liezl KrugmannHolistic Drug Discovery and Development (H3D) Centre, University of Cape Town, Cape Town, South Africa.ORCID https://orcid.org/0000-0003-0089-2136
Kelly ChibaleSouth African Medical Research Council Drug Discovery and Development Research Unit, Department of Chemistry and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.ORCID https://orcid.org/0000-0002-4541-646X

Funding

Repurposing kinase inhibitor chemotypes as antimalarialsR01AI152092 · NIAID · UNIVERSITY OF CAPE TOWN · PI CHIBALE, KELLY, FERRINS, LORI · 2020 to 2024
$1.6M
NIAID NIH HHS R01 AI152092
6 · The paper itself

Abstract

Repurposing drugs whose clinical safety has been established offers a valuable approach to reduce the cost and time associated with the development of new drugs for malaria. Here, we investigate the potential to repurpose the anticancer kinase inhibitor berzosertib for the treatment of malaria, by assessing whether a predicted efficacious human dose for malaria is within the clinically established safety and tolerability profile. First, an oral dose fractionation study was performed in a Plasmodium falciparum-infected humanized mouse model to evaluate the antimalarial pharmacokinetic-pharmacodynamic properties of berzosertib. The activity of berzosertib was shown to be strongly dependent on the time in which the concentrations remain above the minimum parasiticidal concentration (MPC). A human physiologically based pharmacokinetic model was then developed and used to simulate the exposure-response relationships and determine the effective human dose which fulfilled the target pharmacokinetic profile of sustained concentrations above the MPC. Our prediction indicates that six daily intravenous doses of 75 mg of berzosertib will be required for the treatment of an uncomplicated blood stage malaria infection, which is comparatively lower than the clinical maximum tolerated dose for cancer therapy, which was identified as 440 mg administered intravenously twice weekly over a 21-day cycle for up to 18 weeks. Despite berzosertib's potential for repurposing, further preclinical development is necessary to ensure it meets the standard of current and emerging antimalarials.

Identifiers

PMID42080628
PMCPMC13339404

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.