The FieldTemplater is especially valuable for targets, which lack an x-ray crystallographic structure, such as G protein-coupled receptors (GPCRs). Lead optimisation studies supported by knowledge of the bound conformation result in more focussed innovation and accelerated time lines.
To underlie their importance, more than half the blockbuster drugs in the pharmaceutical industry are targeting just two classes of membrane proteins: ion channels and GPCRs.
Ion channels are membrane proteins that enable rapid movement of ions into and out of cells. They are central to the properties of excitable cells, such as those of the nervous system and muscle.
Movement of ions through channels enables such cells to transmit signals through changes in voltage across their membranes. The dysfunction of ion channels is associated with a number of diseases, such as epilepsy and migraine
Cresset's technology is a valuable addition to the in silico research. It is a powerful, automated tool that allows users to develop a model of the bound conformation of active molecules by comparing the molecular fields of compounds known to bind to the same biological target.
"Cresset's Field technology redefines the way medicinal and computational chemists look at molecular structures," said Dr Andy Vinter, Cresset's Founder and CSO.
"With the launch of FieldTemplater we hope to revolutionise the way we do GPCR and ion channel drug discovery, bringing it into the realm of Structure-Based Drug Design," he added.
Cresset's Field technology defines why two structurally different drug molecules can have the same therapeutic effect. If these two compounds bind to the same region of a protein, their 'outer skins' must be similar despite their structural differences.
Cresset has developed technology to create accurate fields around a molecule (the 'skin') by questioning and improving the fundamental science behind their generation.
FieldTemplater is based on Cresset's method of modelling compounds in terms of their molecular fields rather than their atom and bond representations which chemists are accustomed to using.
Approximately 1,000 GPCRs exist, involved in a wide variety of body processes from vision to sexual development as well as many endocrinological and autoimmune disorders.
Among the 100 top-selling drugs, 15 are ion-channel modulators that represent a total market value well in excess of $15 billion (€12.6 billion)
Recent breakthroughs in structural analysis, high-throughput screening, model systems, and molecular genetics have served to minimise the barriers to drug discovery and development that historically have plagued the ion-channel field.