A pilot project aimed at identifying new drug candidates for central nervous system disorders, initiated by Germany's 4SC and Spain's Esteve, has grown into a full-blown collaboration between the companies.
The pilot project identified hits against one Esteve drug target within three months, prompting a larger-scale collaboration involving additional targets, according to the companies.
Under the terms of the agreement, 4SC will use its in silico High Throughput Screening technology, 4Scan, to evaluate a pool of 3.3 million small organic molecules for their potency. This allows the "virtual" prediction of efficacy of molecules based on protein structures, homology modeling, or the biological activity of existing compounds. Suitable hits will then be turned into drug leads through chemical optimisation work conducted by both companies.
After screening, the 4Scan system ranks the compounds in order of their expected biological activity to allow selection for in vitro assay work. Based on the active molecules identified in this first cycle, 4SC's medicinal chemists design virtual combinatorial libraries conserving the pharmacophore pattern of the initial hits.
The system then uses in silico absorption, distribution, metabolism, excretion and toxicology (ADMET) tools to filter out molecules with undesired solubility, membrane permeability or metabolic instability. Those that make it through this process are tested in vitro once again, and the cycle is continued until potential lead series are uncovered.
The initial term of the collaboration with Esteve is 12 months. Financial terms have not been disclosed.