The Medicinal Chemistry (MedChem) Core has been formed to address the urgent need for novel antibacterial agents. The MedChem Core will work seamlessly with the Project Teams and other Cores to drive the time- and cost-efficient discovery and development of novel lead compounds to target high-threat bacterial infections. Critical to its mission are its competencies in industrial and academic medicinal chemistry, cheminformatics, and structural biology, which are complemented by decades of experiences with the fundamental biology of the relevant bacterial agents. The MedChem Core will aid in the confirmation of hits discovered through computation or experimental screens, evolve these to early and then optimized leads following a defined workflow with quantitative metrics for molecules at each stage in the process. The MedChem Core will collaborate on projects focused on the discovery and development of A) phloroglucinol and myxopyronin antibacterials, B) rifamycin and oxazolidinone agents against Mycobacterium abscessus, C) antituberculars targeting cell wall biosynthesis or respiration, D) antibiotics suggested by mining of biosynthetic gene clusters, and E) bacterial cell envelope biogenesis inhibitors to prevent Gram-negative multi-drug resistant infections.
The Medicinal Chemistry (MedChem) Core will provide medicinal chemistry, cheminformatics, and structural biology resources complementary to those existing within the respective project teams. The MedChem Core resource will distinguish itself by relying on extensive pharmaceutical medicinal chemistry experience melded with an academic foundation in antibacterials. Overall, the spectrum and depth of the MedChem Core staff's academic and industrial background will prove critical to their ability to translate basic scientific discoveries within the individual Projects to molecules with significant potential for positively impacting the antibacterial clinical landscape to address the global health crisis.