Integration of Lead Discovery Tactics and the Evolution of the Lead Discovery Toolbox

Selecting Approaches for Hit Identification and Increasing Options by Building the Efficient Discovery of Actionable Chemical Matter from DNA-Encoded Libraries

“…One final factor to bear in mind is that there is inevitably a constraint within any organization that comes with considering a portfolio of programs in a holistic manner and fitting them within the capacity of the available capital resources, flexible budget, and colleague expertise. We acknowledge that in an ideal situation, parallel approaches to hit ID will often lead to novel insights through integration of complementary data sets, an advantage that is well described by Leveridge et al; 51 however, in a world of restricted budgets and pressures to deliver clinical candidates with lean investments, we often find that we are required to limit the number of arms to our hit ID strategies and prioritize resources accordingly. With this in mind, we sought to enhance the impact of our DEL platform in order to fully exploit its unique combination of attributes.…”

Mechanism of Action and Target Identification: A Matter of Timing in Drug Discovery

“…This could reduce the probability of dialing out ll OPEN ACCESS iScience 23, 101487, September 25, 2020 potential side effects, as the target(s) and off-target(s) are hidden. In addition, although more hits are generally recovered from phenotypic screens as mentioned earlier, having multiple chemical entities in hand may offer difficulties in choosing the best lead to optimize (Leveridge et al, 2018). Moreover, TID is a complex and resource-intensive process that can take years or decades to solve (MedChemComm Editorial, 2014;Lederman, 2014).…”

“…Drug discovery has evolved from the identification of active substances in traditional medicines to the direct search for new medicines using high-throughput screening campaigns, fragment-based screening, virtual screening, and other approaches ( Leveridge et al., 2018 ). However, under debate are questions regarding the importance of revealing the specific molecular target and mechanism of action (MoA) for a new drug, and when during the process of drug discovery should such information should be obtained.…”

Molecular targets for the development of new acaricides againstRhipicephalus microplus: a review

“…A promising strategy for the research of new active compounds is the application of in silico methods, such as screening by fragment, pharmacophore models and molecular docking (Leveridge et al ., 2018). These analyses allow one to evaluate the prediction of potential ligand–target interactions, requiring the characterization of molecular targets (protein, receptors) (Davis, 2020).…”