Drug discovery for parasitic diseases: powered by technology, enabled by pharmacology, informed by clinical science

Discovery and Preclinical Pharmacology of INE963, a Potent and Fast-Acting Blood-Stage Antimalarial with a High Barrier to Resistance and Potential for Single-Dose Cures in Uncomplicated Malaria

(2022) Benjamin R. Taft et al.   JOURNAL OF MEDICINAL CHEMISTRY

Plasmodium vivax latent liver infection is characterized by persistent hypnozoites, hypnozoite-derived schizonts and time-dependent efficacy of primaquine

(2022) Erika L. Flannery et al.   Molecular Therapy-Methods & Clinical Development

MalDA, Accelerating Malaria Drug Discovery

(2021) Tuo Yang et al.   TRENDS IN PARASITOLOGY

Opportunities and Challenges in Developing a Cryptosporidium Controlled Human Infection Model for Testing Antiparasitic Agents

(2021) Rajiv S. Jumani et al.   ACS Infectious Diseases

Efficacy of cipargamin (KAE609) in a randomized, Phase II dose-escalation study in adults in sub-Saharan Africa with uncomplicated Plasmodium falciparum malaria

(2021) Esther K Schmitt et al.   CLINICAL INFECTIOUS DISEASES

Lessons learned from the COVID-19 pandemic and its impact on bioanalysis and drug development

(2021) Enaksha R Wickremsinhe et al.   Bioanalysis

DNDI-6148: A Novel Benzoxaborole Preclinical Candidate for the Treatment of Visceral Leishmaniasis

(2021) Charles E. Mowbray et al.   JOURNAL OF MEDICINAL CHEMISTRY

Hepatic safety and tolerability of cipargamin (KAE609), in adult patients with Plasmodium falciparum malaria: a randomized, phase II, controlled, dose-escalation trial in sub-Saharan Africa

(2021) Gilles Ndayisaba et al.   MALARIA JOURNAL

What risks should be permissible in controlled human infection model studies?

(2020) Ariella Binik   BIOETHICS

Biased Diversity for Effective Virtual Screening

(2020) Eric J. Martin et al.   Journal of Chemical Information and Modeling

Liver Enzyme Elevations in Plasmodium falciparum Volunteer Infection Studies: Findings and Recommendations

(2020) Mohamed Farouk Chughlay et al.   AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE

Bumped Kinase Inhibitors as therapy for apicomplexan parasitic diseases: lessons learned

(2020) Ryan Choi et al.   INTERNATIONAL JOURNAL FOR PARASITOLOGY

Establishment, optimisation and quantitation of a bioluminescent murine infection model of visceral leishmaniasis for systematic vaccine screening

(2020) Han Boon Ong et al.   Scientific Reports

Safety, pharmacokinetics and causal prophylactic efficacy of KAF156 in a Plasmodium falciparum human infection study

(2020) James G Kublin et al.   CLINICAL INFECTIOUS DISEASES

Discovery and Characterization of Clinical Candidate LXE408 as a Kinetoplastid-Selective Proteasome Inhibitor for the Treatment of Leishmaniases

(2020) Advait Nagle et al.   JOURNAL OF MEDICINAL CHEMISTRY

Assays for quantification of male and female gametocytes in human blood by qRT-PCR in the absence of pure sex-specific gametocyte standards

(2020) Claire Y. T. Wang et al.   MALARIA JOURNAL

Targeting the trypanosome kinetochore with CLK1 protein kinase inhibitors

(2020) Manuel Saldivia et al.   Nature Microbiology

Functional Genomics for Target Identification

(2020) Davide Gianni et al.   SLAS Discovery

The global, regional, and national burden of leishmaniasis: An ecological analysis from the Global Burden of Disease Study 1990-2017

(2020) Christian J. Scheufele et al.   JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

Bicyclic azetidines kill the diarrheal pathogen Cryptosporidium in mice by inhibiting parasite phenylalanyl-tRNA synthetase

(2020) Sumiti Vinayak et al.   Science Translational Medicine

Rapid and quantitative antimalarial drug efficacy testing via the magneto-optical detection of hemozoin

(2020) Petra Molnár et al.   Scientific Reports

A machine learning approach to define antimalarial drug action from heterogeneous cell-based screens

(2020) George W. Ashdown et al.   Science Advances

Defining the Antimalarial Activity of Cipargamin in Healthy Volunteers Experimentally Infected with Blood-Stage Plasmodium falciparum

(2020) James S. McCarthy et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Drug development post COVID-19 pandemic: toward a better system to meet current and future global health challenges

(2020) Koippallil Gopalakrishnan Aghila Rani et al.   Expert Opinion on Drug Discovery

Identifying purine nucleoside phosphorylase as the target of quinine using cellular thermal shift assay

(2019) Jerzy M. Dziekan et al.   Science Translational Medicine

Lysyl-tRNA synthetase as a drug target in malaria and cryptosporidiosis

(2019) Beatriz Baragaña et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Optimization of Methionyl tRNA-Synthetase Inhibitors for Treatment of Cryptosporidium Infection

(2019) Frederick S. Buckner et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

The Evolution of High-Throughput Experimentation in Pharmaceutical Development, and Perspectives on the Future

(2019) Steven M Mennen et al.   ORGANIC PROCESS RESEARCH & DEVELOPMENT

Preclinical candidate for the treatment of visceral leishmaniasis that acts through proteasome inhibition

(2019) Susan Wyllie et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Next-Generation Phenotypic Screening in Early Drug Discovery for Infectious Diseases

(2019) Nathalie Aulner et al.   TRENDS IN PARASITOLOGY

Identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis

(2019) Christopher S. Lunde et al.   Nature Communications

All-Assay-Max2 pQSAR: Activity Predictions as Accurate as Four-Concentration IC50s for 8558 Novartis Assays

(2019) Eric J. Martin et al.   Journal of Chemical Information and Modeling

Mass spectrometry-based Cellular Thermal Shift Assay (CETSA®) for target deconvolution in phenotypic drug discovery

(2019) Tomas Friman   BIOORGANIC & MEDICINAL CHEMISTRY

In vitro selection predicts malaria parasite resistance to dihydroorotate dehydrogenase inhibitors in a mouse infection model

(2019) Rebecca E. K. Mandt et al.   Science Translational Medicine

Setting Our Sights on Infectious Diseases

(2019) Manu De Rycker et al.   ACS Infectious Diseases

Model-Informed Drug Development for Malaria Therapeutics

(2018) Kayla Ann Andrews et al.   Annual Review of Pharmacology and Toxicology

In Vitro Culture, Drug Sensitivity, and Transcriptome of Plasmodium Vivax Hypnozoites

(2018) Nil Gural et al.   Cell Host & Microbe

Development of Trypanosoma cruzi in vitro assays to identify compounds suitable for progression in Chagas’ disease drug discovery

(2018) Lorna M. MacLean et al.   PLoS Neglected Tropical Diseases

Spontaneous dormancy protects Trypanosoma cruzi during extended drug exposure

(2018) Fernando J Sánchez-Valdéz et al.   eLife

Innovation in neglected tropical disease drug discovery and development

(2018) Hong-Bo Weng et al.   Infectious Diseases of Poverty

Development of a Cytopathic Effect-Based Phenotypic Screening Assay against Cryptosporidium

(2018) Alexander T. Chao et al.   ACS Infectious Diseases

Phase I/II Evaluation of the Prophylactic Antimalarial Activity of Pafuramidine in Healthy Volunteers Challenged with Plasmodium falciparum Sporozoites

(2018) Myaing M. Nyunt et al.   AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE

Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis

(2018) Susan Wyllie et al.   NATURE

Clinical and veterinary trypanocidal benzoxaboroles target CPSF3

(2018) Richard J. Wall et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

QSAR-Based Virtual Screening: Advances and Applications in Drug Discovery

(2018) Bruno J. Neves et al.   Frontiers in Pharmacology

Drug Discovery for Kinetoplastid Diseases: Future Directions

(2018) Srinivasa P. S. Rao et al.   ACS Infectious Diseases

A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis

(2017) Ujjini H. Manjunatha et al.   NATURE

Plasmodium vivax Controlled Human Malaria Infection – Progress and Prospects

(2017) Ruth O. Payne et al.   TRENDS IN PARASITOLOGY

A potent antimalarial benzoxaborole targets a Plasmodium falciparum cleavage and polyadenylation specificity factor homologue

(2017) Ebere Sonoiki et al.   Nature Communications

Estimation of the in-vivo minimum inhibitory concentration of cipargamin in uncomplicated Plasmodium falciparum malaria

(2016) Hien Tinh Tran et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness

(2016) Shilpi Khare et al.   NATURE

Antimalarial Activity of KAF156 in Falciparum and Vivax Malaria

(2016) Nicholas J. White et al.   NEW ENGLAND JOURNAL OF MEDICINE

The Burden of Cryptosporidium Diarrheal Disease among Children < 24 Months of Age in Moderate/High Mortality Regions of Sub-Saharan Africa and South Asia, Utilizing Data from the Global Enteric Multicenter Study (GEMS)

(2016) Samba O. Sow et al.   PLoS Neglected Tropical Diseases

Assessing anti- T. cruzi candidates in vitro for sterile cidality

(2016) Monica Cal et al.   International Journal for Parasitology-Drugs and Drug Resistance

UDP-galactose and acetyl-CoA transporters as Plasmodium multidrug resistance genes

(2016) Michelle Yi-Xiu Lim et al.   Nature Microbiology

When Quality Beats Quantity: Decision Theory, Drug Discovery, and the Reproducibility Crisis

(2016) Jack W. Scannell et al.   PLoS One

Limited Ability of Posaconazole To Cure both Acute and Chronic Trypanosoma cruzi Infections Revealed by Highly SensitiveIn VivoImaging

(2015) Amanda Fortes Francisco et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Gift from Nature: Cyclomarin A Kills Mycobacteria and Malaria Parasites by Distinct Modes of Action

(2015) Nathalie Bürstner et al.   CHEMBIOCHEM

A novel multiple-stage antimalarial agent that inhibits protein synthesis

(2015) Beatriz Baragaña et al.   NATURE

Drug discovery for the developing world: progress at the Novartis Institute for Tropical Diseases

(2015) Catherine L. Jones et al.   NATURE REVIEWS DRUG DISCOVERY

Utilizing Chemical Genomics to Identify Cytochrome b as a Novel Drug Target for Chagas Disease

(2015) Shilpi Khare et al.   PLoS Pathogens

No more monkeying around: primate malaria model systems are key to understanding Plasmodium vivax liver-stage biology, hypnozoites, and relapses

(2015) Chester Joyner et al.   Frontiers in Microbiology

Development and application of a sensitive, phenotypic, high-throughput image-based assay to identify compound activity against Trypanosoma cruzi amastigotes

(2015) Melissa L. Sykes et al.   International Journal for Parasitology-Drugs and Drug Resistance

KAF156 Is an Antimalarial Clinical Candidate with Potential for Use in Prophylaxis, Treatment, and Prevention of Disease Transmission

(2014) Kelli L. Kuhen et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Identification of Plasmodium PI4 kinase as target of MMV390048 by chemoproteomics

(2014) Sonja Ghidelli-Disse et al.   MALARIA JOURNAL

Spiroindolone KAE609 for Falciparum and Vivax Malaria

(2014) Nicholas J. White et al.   NEW ENGLAND JOURNAL OF MEDICINE

Randomized Trial of Posaconazole and Benznidazole for Chronic Chagas' Disease

(2014) Israel Molina et al.   NEW ENGLAND JOURNAL OF MEDICINE

(+)-SJ733, a clinical candidate for malaria that acts through ATP4 to induce rapid host-mediated clearance ofPlasmodium

(2014) María Belén Jiménez-Díaz et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates

(2014) J. Straimer et al.   SCIENCE

Drug Repurposing Screen Reveals FDA-Approved Inhibitors of Human HMG-CoA Reductase and Isoprenoid Synthesis That Block Cryptosporidium parvum Growth

(2013) Kovi Bessoff et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Fast in vitro methods to determine the speed of action and the stage-specificity of anti-malarials in Plasmodium falciparum

(2013) Claire Le Manach et al.   MALARIA JOURNAL

Designing the next generation of medicines for malaria control and eradication

(2013) Jeremy N Burrows et al.   MALARIA JOURNAL

Targeting Plasmodium PI(4)K to eliminate malaria

(2013) Case W. McNamara et al.   NATURE

Highly Sensitive In Vivo Imaging of Trypanosoma brucei Expressing “Red-Shifted” Luciferase

(2013) Alex P. McLatchie et al.   PLoS Neglected Tropical Diseases

Selective and Specific Inhibition of the Plasmodium falciparum Lysyl-tRNA Synthetase by the Fungal Secondary Metabolite Cladosporin

(2012) Dominic Hoepfner et al.   Cell Host & Microbe

Mass Spectrometry-Based Proteomics in Preclinical Drug Discovery

(2012) Markus Schirle et al.   CHEMISTRY & BIOLOGY

Development of humanized mouse models to study human malaria parasite infection

(2012) Ashley M Vaughan et al.   Future Microbiology

High-throughput decoding of antitrypanosomal drug efficacy and resistance

(2012) Sam Alsford et al.   NATURE

Profile-QSAR: A Novelmeta-QSAR Method that Combines Activities across the Kinase Family To Accurately Predict Affinity, Selectivity, and Cellular Activity

(2011) Eric Martin et al.   Journal of Chemical Information and Modeling

A new molecular approach for cidal vs static antimalarial determination by quantifying mRNA levels

(2011) Noemí Bahamontes-Rosa et al.   MOLECULAR AND BIOCHEMICAL PARASITOLOGY

How were new medicines discovered?

(2011) David C. Swinney et al.   NATURE REVIEWS DRUG DISCOVERY

Towards an In Vitro Model of Plasmodium Hypnozoites Suitable for Drug Discovery

(2011) Laurent Dembele et al.   PLoS One

SCYX-7158, an Orally-Active Benzoxaborole for the Treatment of Stage 2 Human African Trypanosomiasis

(2011) Robert T. Jacobs et al.   PLoS Neglected Tropical Diseases

Spiroindolones, a Potent Compound Class for the Treatment of Malaria

(2010) M. Rottmann et al.   SCIENCE