In 2013, H3D was awarded funding by the Bill & Melinda Gates Foundation (BMGF) for malaria and TB drug discovery and, subsequently, was elected to the Tuberculosis Drug Accelerator consortium (TBDA) in 2014. Within the context of the TBDA, further collaborations were initiated with the Infectious Disease Research Institute (IDRI) and Elli Lilly, as well as Celgene Global Health. H3D also partnered with the HIT-TB consortium, taking advantage of collaborations with NIH research groupings as well as leading public and private institutions in exploring advanced research models to identify new medicines to treat TB.
H3D has established medium-throughput screening platform for phenotypic- as well as target-based screening to identify novels hits for lead generation programs. In addition, multiple chemical series identified from phenotypic- and target-based screening of pharmaceutical company libraries are being evaluated to generate a panel of mechanistically distinct chemical series potentially effective against TB.
In the spirit of “Team TBDA”, H3D has partnered with Evotec, Texas A&M University and other TBDA members to collaboratively prosecute a target-based project towards novel inhibitors of Mtb RNA Polymerase to combat TB.
Select H3D TB Publications:
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1,3-Diarylpyrazolyl-acylsulfonamides as Potent Anti-tuberculosis Agents Targeting Cell Wall Biosynthesis in Mycobacterium tuberculosis J. Med. Chem. 2021, 64, 12790−12807; PMID: 34414766; DOI: 10.1021/acs.jmedchem.1c00837.
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Antitubercular 2-Pyrazolylpyrimidinones: Structure-Activity Relationship and Mode-of-Action Studies. J. Med. Chem. 2021, 64, 719−740; PMID: 33395287; PMC: PMC7816196; DOI: 10.1021/acs.jmedchem.0c01727.
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Benzoheterocyclic Oxime Carbamates Active against Mycobacterium tuberculosis: Synthesis, Structure–Activity Relationship, Metabolism, and Biology Triaging. Journal of Medicinal Chemistry. 2021, 64, 13, 9444–9457.
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Strategies to Combat Multi-Drug Resistance in Tuberculosis. Accounts of Chemical Research. 2021, 54, 10, 2361–2376
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Novel Antitubercular 6-Dialkylaminopyrimidine Carboxamides from Phenotypic Whole-Cell High Throughput Screening of a SoftFocus Library: Structure-Activity Relationship and Target Identification Studies. J. Med. Chem. 2017, 60, 10118−10134; PMID: 29148755; PMC: PMC5748279; DOI: 10.1021/acs.jmedchem.7b01347.
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Pyrrolo[3,4-c]pyridine-1,3(2H)-diones: A Novel Antimycobacterial Class Targeting Mycobacterial Respiration J. Med. Chem. 2015, 58, 9371-9381; PMID: 26551248; DOI: 10.1021/acs.jmedchem.5b01542
For more information on our available TB assays please see here
