Delving into the Latest Updates on BRD-7929 with Synapse

Bicyclic azetidine compounds possess antimalarial activity via targeting of the cytoplasmic Plasmodium falciparum (Pf) protein translation enzyme phenylalanine-tRNA synthetase (cFRS). These drugs kill parasites both in vitro and in vivo, including the blood, liver, and transmission developmental stages. Here we present the co-crystal structure of PfcFRS with a potent inhibitor, the bicyclic azetidine BRD7929. Our studies reveal high-affinity binding of BRD7929 with PfcFRS along with exquisite specificity compared with the human enzyme, leading in turn to potent and selective inhibition of the parasite enzyme. Our co-crystal structure shows that BRD7929 binds in the active site in the α subunit of PfcFRS, where it occupies the amino acid site, an auxiliary site, and partially the ATP site. This structural snapshot of inhibitor-bound PfcFRS thus provides a platform for the structure-guided optimization of novel antimalarial compounds.

01 Nov 2016·Nature Reviews Drug Discovery

Novel antimalarial target identified

Article

Author: Crunkhorn, Sarah

This short article discusses the identification of a bicyclic azetidine BRD7929 which prevented disease transmission, ensured prophylaxis and displayed single low-dose cure, with activity against all Plasmodium parasite life stages.

100 Deals associated with BRD-7929

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Cryptosporidiosis	Preclinical	US	The Broad Institute, Inc.	30 Sep 2020
Cryptosporidiosis	Preclinical	NL	TropIQ Health Sciences BV	30 Sep 2020
Cryptosporidiosis	Preclinical	US	University of Illinois At UrbanaChampaign	30 Sep 2020
Cryptosporidiosis	Preclinical	CN	WuXi AppTec Co., Ltd.	30 Sep 2020
Cryptosporidiosis	Preclinical	CN	Eisai China, Inc.	30 Sep 2020