Delving into the Latest Updates on SWJM-992 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

PfATP4

Mechanism

PfATP4 inhibitors(P. falciparum P-type ATPase 4 inhibitors)

Therapeutic Areas

Infectious Diseases

Active Indication

Malaria

Inactive Indication-

Originator Organization

University of Melbourne

Active Organization

TCG Lifesciences Pvt Ltd.

The Walter & Eliza Hall Institute of Medical Research

University of Melbourne

+ [1]

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Author: Chowdury, Mrittika ; Ashton, Trent D. ; Jarman, Kate E. ; Calic, Petar P. S. ; Brand, Stephen ; Giannangelo, Carlo ; Sleebs, Brad E. ; de Koning-Ward, Tania F. ; Famodimu, Mufuliat T. ; MacRaild, Christopher A. ; Pollard, Harry ; Cowman, Alan F. ; Ooi, Zi Kang ; Sutherland, Colin J. ; Gancheva, Maria R. ; Dans, Madeline G. ; Jackson, Paul F. ; Lehane, Adele M. ; Baud, Delphine ; Loi, Katie ; Zhou, Qingmiao ; Creek, Darren J. ; Qiu, Deyun ; Delves, Michael J. ; De, Nirupam ; Palandri, Josephine ; Mao, Emma Y. ; Wilson, Danny W. ; Maity, Bikash Chandra

To contribute to the global effort to develop new antimalarial therapies, we previously disclosed initial findings on the optimization of the dihydroquinazolinone-3-carboxamide class that targets PfATP4. Here we report on refining the aqueous solubility and metabolic stability to improve the pharmacokinetic profile and consequently in vivo efficacy. We show that the incorporation of heterocycle systems in the 8-position of the scaffold was found to provide the greatest attainable balance between parasite activity, aqueous solubility, and metabolic stability. Optimized analogs, including the frontrunner compound S-WJM992, were shown to inhibit PfATP4-associated Na⁺-ATPase activity, gave rise to a metabolic signature consistent with PfATP4 inhibition, and displayed altered activities against parasites with mutations in PfATP4. Finally, S-WJM992 showed appreciable efficacy in a malaria mouse model and blocked gamete development preventing transmission to mosquitoes. Importantly, further optimization of the dihydroquinazolinone class is required to deliver a candidate with improved pharmacokinetic and risk of resistance profiles.

100 Deals associated with SWJM-992

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Malaria	Preclinical	CH	MMV Medicines for Malaria Venture	12 Aug 2024
Malaria	Preclinical	IN	TCG Lifesciences Pvt Ltd.	12 Aug 2024
Malaria	Preclinical	AU	The Walter & Eliza Hall Institute of Medical Research	12 Aug 2024
Malaria	Preclinical	AU	University of Melbourne	12 Aug 2024