SC83288 is a clinical development candidate for the treatment of severe malaria

Stefano Pegoraro (), Maëlle Duffey, Thomas D Otto, Yulin Wang, Roman Rösemann, Roland Baumgartner, Stefanie K Fehler, Leonardo Lucantoni, Vicky M Avery, Alicia Moreno-Sabater, Dominique Mazier, Henri J Vial, Stefan Strobl, Cecilia P Sanchez and Michael Lanzer ()
Additional contact information
Stefano Pegoraro: 4SC AG, Am Klopferspitz 19a
Maëlle Duffey: Parasitology, Universitätsklinikum Heidelberg
Thomas D Otto: Parasite Genomics, Wellcome Trust Sanger Institute, Wellcome Genome Campus
Yulin Wang: Parasitology, Universitätsklinikum Heidelberg
Roman Rösemann: 4SC Discovery GmbH, Am Klopferspitz 19a
Roland Baumgartner: 4SC AG, Am Klopferspitz 19a
Stefanie K Fehler: 4SC AG, Am Klopferspitz 19a
Leonardo Lucantoni: Eskitis Institute for Drug Discovery, Griffith University, Don Young
Vicky M Avery: Eskitis Institute for Drug Discovery, Griffith University, Don Young
Alicia Moreno-Sabater: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 Bd de l’hôpital
Dominique Mazier: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 Bd de l’hôpital
Henri J Vial: Dynamique des Interactions Membranaires Normales et Pathologiques, CNRS UMR 5235, Université Montpellier II
Stefan Strobl: 4SC Discovery GmbH, Am Klopferspitz 19a
Cecilia P Sanchez: Parasitology, Universitätsklinikum Heidelberg
Michael Lanzer: Parasitology, Universitätsklinikum Heidelberg

Nature Communications, 2017, vol. 8, issue 1, 1-17

Abstract: Abstract Severe malaria is a life-threatening complication of an infection with the protozoan parasite Plasmodium falciparum, which requires immediate treatment. Safety and efficacy concerns with currently used drugs accentuate the need for new chemotherapeutic options against severe malaria. Here we describe a medicinal chemistry program starting from amicarbalide that led to two compounds with optimized pharmacological and antiparasitic properties. SC81458 and the clinical development candidate, SC83288, are fast-acting compounds that can cure a P. falciparum infection in a humanized NOD/SCID mouse model system. Detailed preclinical pharmacokinetic and toxicological studies reveal no observable drawbacks. Ultra-deep sequencing of resistant parasites identifies the sarco/endoplasmic reticulum Ca2+ transporting PfATP6 as a putative determinant of resistance to SC81458 and SC83288. Features, such as fast parasite killing, good safety margin, a potentially novel mode of action and a distinct chemotype support the clinical development of SC83288, as an intravenous application for the treatment of severe malaria.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms14193 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14193

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms14193

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().