Hit to Lead and Lead Optimization Services

After initial biological testing of selected compounds, the verified hits often undergo hit-to-lead analysis in order to progress several sets of compounds into just a few preclinical candidates.

Drug leads design

We design lead series for the target on the basis of verified hits, provided by a close collaboration between our partners and chemistry teams, in two steps:

1. Creating new targeted libraries on the basis of hits verified in the initial biological testing stage.

2. Carrying out in silico screening of these compounds against the target.

ADME Modeling

Physiologically-based pharmacokinetic modeling (PBPK) is a mathematical modeling technique to predict Absorption, Distribution, Metabolism and Excretion (ADME) of a compound in the body and is used in pharmaceutical research.

ADME describes the ability of a potential new drug compound to performe a pharmacological activity.

Our computer calculations will help you to estimate preclinical or non-clinical ADME parameters including:

  • Absorption – maximum fraction absorbed, fraction absorbed, bioavailability.
  • Distribution – partition coefficients and volume of distribution in steady state, concentration-time curves in plasma and organs, active transport.
  • Metabolism – predicting pharmacokinetic behavior on the basis of metabolism rates.
  • Excretion – ways of excretion, enterohepatic cycle.
  • Sensitivity analysis for interactions and individual variations.
  • Pharmaceutical application – assessment of the best pharmaceutical form.

Quantitative Drug toxicity prediction (including LD50)

Our protocols have been developed to provide quantitative information for early assessment of compound toxicity and include:

1. MRTD – maximum recommended therapeutic dose, MRDD – maximum recommended daily allowance, LD50.

2. To characterize the toxicity of a drug lead we screen the compound against a panel of more than 200 human proteins to characterize the toxicity of the compound.

This service predicts drug toxicity and LD50. First, a toxicological profile is predicted by in silico screening of a drug candidate molecule against hundreds of diverse proteins representing different active site types of the human proteome. The active site types that show high affinity for a compound (IC50) are considered as sensitive. In the second round of the toxicity assessment procedure, all proteins similar to those with the sensitive active site types are included in screening. As a result, we obtain IC50 (IC50, represents the concentration of an inhibitor that is required for 50% inhibition of its target) of a tested compound for every protein from our toxicological protein platform. On the basis of this information we draw a conclusion about adverse reaction targets of a compound and its possible adverse effects.