Novel Research: Hit to Lead

 It is important to set clear go/no-go criteria for the progression of hit and lead compounds. A high throughput screening (hts) hit, was optimized and evaluated for the enzymatic inhibition of plk-1 kinase. Molecular modeling suggested the importance of adding a hydrophobic aromatic amine side chain in order to improve the potency by a classic kinase h-donor-acceptor binding mode.  A target is a broad term which can be applied to a range of biological entities which may include for example proteins, genes and RNA. A good target needs to be efficacious, safe, meet clinical and commercial needs and, above all, be ‘druggable’.g-protein-coupled receptors (gpcrs), whereas antibodies are good at blocking protein/protein interactions. Once identified, the target then needs to be fully prosecuted. Validation techniques range from in vitro tools through the use of whole animal models, to modulation of a desired target in disease patients.

  • High throughput screening
  • Target identification
  • Target validation
  • Assay development
  • Screening cascade-Lead optimization

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