Allinky's technology platform for in silico drug design focuses on the discovery of allosteric drugs. These drugs interfere with the conformational structure of a given target protein or with its capacity to interact with surrounding proteins. Once a lead compound for a given target protein is identified, Allinky follows a medicinal chemistry program supported by in vitro and in vivo testing. These compounds are of great relevance for the pharmaceutical industry as well as hopeful treatments for several diseases of great impact.
The Technology Platform can be broken down in four steps:
Computer-based approach to identify target binding interactions and allosteric regulatory pockets;
In silico discovery of small molecules (hits) interacting with target sites and in vitro assay to determine best compounds (leads);
Medicinal chemistry for lead optimization in parallel with crystallography studies and cell-based assays to establish Proof of Principle; and finally
Assessment of best drug candidates in validated animal models and in ADMET studies to establish animal Proof of Concept and pharmacokinectics properties.
QSAR (Quantitative Structure Analysis Relation)
Allinky has developed a robust approach for the hit-to-lead development based on pharmacophore optimization combined with specific docking algorithms to understand the key features of the ligand-target biomolecule interaction. These capabilities have been proved successful for the development of protein-protein and allosteric inhibitors. Also, this approach is carried out with a simultaneous assessment of the drug-like features of the molecules.
In vitro and in vivo testing
Allinky has in-house capabilities and extensive know-how to perform robust enzymatic assay with poor solubility chemical compounds in different proteins measuring IC50. Moreover, these compounds are routinely screened in cell-based assays to measure inflammatory mediators, cell survival and/or death in different primary cells and cell lines. Regarding in vivo testing, Allinky has established collaboration with different research groups world-wide to test compounds in validated animal models and xenografts.
Medicinal Chemistry and Crystallography
Traditional organic and combinatorial chemistry practice in Allinky is guided by QSAR analysis and lead-optimization key variables beyond Lipinsky rule of five such as K(i), PSA and MW as well as Ligand Eficiency Indexes (LEI). Allinky has reached agreements with key experts on co-crystallization studies and has access to NMR as well as x-ray facilities for the resolution of ligand-target interaction.