Lead optimization

For the lead optimization process we developed novel and optimized synthetic procedures for large series of core structures. We have established more than 110 core and several hundreds scaffold chemistry, and have >7000 synthetic protocols in hand including stereospecific and stereoselective reactions of heterocycles, regioselective reactions, special coupling reactions, multistep traditional synthesis, reaction in inert atmosphere and microwave assisted reactions.

QSAR and QSPR information from NCL, Master Key and Scaffold Hopping platforms contributes to accelerated lead optimization. Our pharmacophore model identifies subsituents and chemical groups contributing to biological activity of compounds based on different scaffolds. Our medicinal chemists use this knowledge for rapid lead compound optimization. We can develop a low nanomolar preclinical candidate lead compound within one year.

ADMET optimization

We use externally validated in silico ADMET models for filtering out druglike compounds from the NCL virtual library. The selected and synthesized novel active derivatives are characterized in experimental ADMET models. The new data obtained are fed back into the computational models in an iterative manner enhancing the reliability of the predictions.

Vichem's approach to the early determination of ADME/Tox properties helps to advance compounds rapidly into preclinical development. Our in vitro assays are capable for the determination of solubility, absorption, metabolic susceptibility, and toxic properties.

We measure the following Experimental ADMET parameters:

• Solubility
• Protein binding
• Permeability (PAMPA, CaCo2)
• Liver microsomal stability
• In vitro intrinsic clearance
• CYP-P450 inhibition
• Glucuronidation
• Hepatocyte (metabolic stability) assay
• In vivo animal toxicity
• AMES test

We can carry our cellular proliferation and apoptotic assays and in vivo assays for various tumor models.