Tripos' program accelerates drug discovery
discovery process. The new program offers a method to develop novel
preclinical compounds for customers in the pharmaceutical and
biotechnology industry.
Tripos has created compound sets that contain novel, selective inhibitors with demonstrated potency and selectivity toward G-protein-coupled receptors (GPCRs) and kinases and have the potential to generate new intellectual property for customers.
Each LeadDiscovery set is based on multiple novel scaffolds that have shown activity and selectivity for the specified gene family in biological assays. These compounds were designed and developed using Tripos' technologies including ChemSpace to identify novel active structures from known leads.
Approximately 30 per cent of all currently marketed drugs act on one or more GPCRs, and kinases play an active role in cancer and inflammatory diseases. This is achieved by either activating the receptors (agonists), or blocking the effects of receptor activation (antagonists).
Tripos, a provider of drug discovery chemistry and informatics solutions, said that the LeadDiscovery research would be expected to expand into programs for ion channels and proteases.
"LeadDiscovery provides Tripos and its customers with commercialisation opportunities at a time when the pharmaceutical industry is looking for early-stage drug candidates that have achieved proof of principle and are more likely to enter the clinical phase," said John McAlister, president and CEO of Tripos.
Applying informatics along the discovery process can reduce the time taken in each phase, both by exploiting mining to reduce the attrition of candidate compounds and by managing the logistics of the whole process. Estimates have placed the time taken from initial screening to a preclinical drug candidate reduced to 9-18 months from an industry standard of 2½-3 years.
Pharmaceutical and biotech companies can access Tripos' LeadDiscovery compounds for screening against their own targets at their research laboratories, and may elect to acquire ownership rights from Tripos for selected compounds.
"Our new LeadDiscovery program provides customers with access to leads through a low-risk, high-return business model," said Mark Allen, senior vice president and general manager of Tripos Discovery Research.
Sales of drugs targeting GPCRs thus constitute a considerable fraction of all drug sales, generating revenues of about $50 billion in 2003. This figure is set to grow as more GPCR receptors become de-orphanised.
One drug from this area is GlaxoSmithKline's (GSK) sumatriptan, a 5-HT1b/1d/1f agonist anti-migraine compound. As more receptor sub-types have become apparent and some drugs have been withdrawn due to toxicity, research has remained intensive in the 5HT area.
More recent 5-HT1D examples of antimigraine therapeutics include AstraZeneca's zolmitriptan (licensed from GSK), a dual action 5-HT1B/1D-receptor agonist and Almirall's selective agonist almotriptan (Axert; Almogran; Amignul).
Selective 5-HT2A receptor antagonists may provide the basis for new therapies for psychosis and drug dependence, in addition to contributing towards a more complete understanding of 5-HT2A receptor functions.
