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bacPROTACs
- Development stage
- Preclinical
- Lead developer
- Foundation for Neglected Disease Research
- Modality
- PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules
01
Overview
bacPROTACs (specifically Homo-BacPROTACs) are a novel class of small molecule degraders being developed by the Foundation for Neglected Disease Research (FNDR) for the treatment of tuberculosis, including multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains. These molecules utilize the Bacterial Proteolysis-Targeting Chimera (bacPROTAC) technology to induce the degradation of ClpC1, an essential ATPase that serves as a chaperone for the ClpP protease complex in *Mycobacterium tuberculosis*. By hijacking the bacteria's own proteolytic machinery, bacPROTACs cause the selective degradation of ClpC1, leading to proteotoxic stress and bacterial cell death. This degradation-based approach offers a distinct advantage over traditional inhibition by potentially overcoming resistance mechanisms and providing more sustained therapeutic effects. The program is currently in the preclinical hit-to-lead stage.
- Other names
- Homo-BacPROTACsClpC1 degradersClpC-1 degradersClpC 1 degradersBacPROTACs
02
Targets
ClpC2 (ATP-dependent protease ATP-binding subunit ClpC2)ClpC1 (Bacterial ClpC1)
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