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Targeting de novo purine biosynthesis for tuberculosis treatment

18 Jun 2025

Abstract excerpt

. Here we report the discovery of a first-in-class small-molecule inhibitor targeting PurF, the first enzyme in the mycobacterial de novo purine biosynthesis pathway. The lead candidate, JNJ-6640, exhibited nanomolar bactericidal activity in vitro. Comprehensive genetic and biochemical approaches confirmed that JNJ-6640 was highly selective for mycobacterial PurF. Single-cell-level microscopy demonstrated a...

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PMID: 40533558
DOI: 10.1038/s41586-025-09177-7

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