The goal of lead optimization is to improve the effectiveness of initial ‘hits’ from primary screening. There are many approaches to lead optimization, all of which have the same theme: reduce off-target effects, create an improved ADME profile and improve a compound’s efficacy.

 

Typically, lead optimization is accomplished by creating many compound analogs of the initial ‘hit’. These analogs are evaluated and those which show promise are moved ahead in the drug development process and are most likely to survive the arduous and expensive stages of preclinical and clinical testing.

 

Caliper provides a comprehensive suite of solutions to help drive your lead optimization programs including, custom designed integrated lab automation, plate handling & liquid handling systems for analog creation and compound management, to instruments specifically designed for drug discovery and drug development. Our LabChip drug discovery systems are based on microfluidics using separations-based mobility-shift for enzymatic assays. This technology yields the highest data quality available on any screening platform to help guide your lead optimization efforts.

 

In addition to providing instruments to automate lead optimization, we offer a comprehensive array of assay services and discovery programs through Caliper Discovery Alliances & Services (CDAS). The early identification and elimination of compounds with toxicity issues saves considerable time, effort and cost in the early stage of drug development. CDAS offers in vitro compound profiling to evaluate a lead candidates safety, selectivity profile and potency early in the development process. Other in vitro CDAS studies to help optimize lead candidate development include cellular toxicity studies such as proliferation/viability, metabolism (cytochrome p450 and drug stability/half-life) and apoptosis testing.

 

Investigation of Structure-Activity Relationships (SAR) is a fundamental activity carried out by medicinal chemists during the process of optimization of hits to lead compounds. CDAS has developed an enhancement to traditional SAR by creating the Side Effect Database™ (SED). The Caliper SED contains in vitro profile data of known compounds such as reference compounds, marketed pharmaceuticals, agrochemicals and more, tested through a broad array of assays (GPCR’s, Ion Channel, Transporter, Nuclear Receptor, Enzymes, etc.). Companies can gain access to the SED via consulting services or alternatively individual compound profiles are available through the SEDSelect™ section of our website.