The dihydroisoquinolones (DHIQ’s), a novel class of antimalarials, were discovered using a phenotypic whole cell screen of erythrocytic co-cultures of malaria.  A consortium of researchers in the academic, for-profit, and non-profit sectors developed the  dihydroisoquinolone clinical candidate SJ733. In preclinical studies, SJ733 had good potency in vitro and in vivo and a fast rate of kill in vivo; was highly orally bioavailable in mice, rats, and dogs; and had mild toxicology in vivo.  SJ733 targets ATP4, a sodium-proton antiporter critical for parasite viability in the blood stages and for gametocyte development.  Phase 1a clinical studies with SJ733 revealed no serious adverse events or dose limiting toxicities; good oral bioavailability, and terminal half-life of 19 hours. Phase 1b studies in the <i>P. falciparum </i>human challenge model showed a fast parasite kill but strongly suggested that curing patients would require at least a 3-day schedule, due to metabolism by CYP3A4.  A recently completed Phase 2a trial in Peru demonstrated that SJ733 monotherapy effectively cured blood stage P. vivax malaria in most cases at 14-days. This study strongly suggests SJ733 is well positioned to be a fast-acting component in a combination drug for treating malaria.

2022 Philip S. Portoghese Journal of Medicinal Chemistry/ACS Medicinal Chemistry Letters/Division of Medicinal Chemistry Joint Lectureship Awards: Discovery and development of the novel antimalarial SJ733

Where thousands of chemistry professionals meet to share ideas and advance scientific and technical knowledge. Spring 2023 abstracts, posters, and presentations will launch at the end of March.

ACS Spring 2023

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.