DDRC uniquely blends core academic strengths with a translation-oriented mindset to chart non-intuitive paths to drug discovery and development. A deep understanding of cell and molecular biology is reinforced through ‘omics’ and other high-throughput approaches, to capture disease-specific molecular perturbations across the temporal scale of disease initiation and progression. Complementation of this activity through development of new tools for precise quantitation and characterization of the perturbations ensures ‘richness’ of the data generated. The complex data that results is then interrogated through the prism of systems biology, by bringing to bear a creative mix of computational and mathematical methodologies. This enables identification first of the core regulatory drivers of the disease process, and then of the driver components that can potentially serve as drug targets.
Potential targets identified are subjected to a rigorous bioassay pipeline, and those that withstand the test of validation are taken up for drug development efforts. A battery of approaches that include X-ray crystallography, computational structural biology, chemoinformatics, and virtual screening, are then converged to empower small molecule inhibitor design; with subsequent synthesis and experimental evaluation of the molecules leading to generation of the ‘first-line’ hits.
The hit-to-lead route is navigated through an SAR analysis, where a robust high-content screening platform facilitates quick selection that – in addition to efficacy – also scores for preliminary PK properties and undesirable phenotypic side effects. We keep an up front emphasis on key safety issues, while striving for high potency, to minimize the iteration rounds necessary. Criteria such as key pharmacophore, structure-associated liabilities, and target selectivity, are carefully scrutinized during the inhibitor development process. From ‘lead’ to a candidate for IND enabling studies – by clearing the barriers of MTD, PK/ADMET optimization, pre-clinical toxicity – then represents the final lap of DDRC’s ambition to contribute to the drug development process.
Complementing these efforts is a strong program that assimilates comprehensive analyses of disease-specific markers through artificial intelligence-based platforms, to generate tools for early diagnosis and prognosis of disease. Such tools would prove equally beneficial for predicting outcome in clinical trials for drugs and vaccines.
DDRC also offers a range of services and facilities to aid both academia and industry in their own drug development programs.