Drugs for Neglected Diseases initiative - DNDi

1. Design and synthesis of Torin2 analogs through multistep synthesis. Targeting PIKK family kinases ( ATR, ATM, mTOR, and DNA-PK's) using novel synthesized Torin2 analogs.. Identification of SPK98 as ATR and mTOR inhibitor, with an increased half-life T ½ of 157 min and internal clearance in mice as compared to Torin2.. Homology modeling of ATR kinaseMolecular docking studies: To rationalize the structure-to-activity relationship of kinase inhibitors2. Developed a simple and efficient, base-free synthesis of pyrazolo[4,3-c] quinoline-3-ones from aryl hydrazines and 4 – chloroquinoline esters and identification of pyrazolo[4,3-c] quinoline-3-ones as PDE5 inhbitors. 3. Small molecule crystallization, structure solving, and investigation of different intermolecular interactions using theoretical and experimental studies.Able to solve crystal structures of a solvated dimer of Gefitinib and its co-formers, Also, solved crystal structures of few drug-like intermediates.4. Design of kinase assays for inhibitor screening/HTS library

. HTS screening of a library of compounds against target kinase. Design and Development of FRET-based constructs to visualize protein-protein interactions in order to assess the relative efficiencies of synthesized molecules against the kinase substrate.

Multi-step synthesis, analysis of intermediates, investigating impurities and process of various bulk drugs and active pharmaceutical ingredients at bench scale.