Kalexsyn, Inc: your science deserves the best scientists

Research Capabilities Computer-Aided Drug Design (CADD)

Kalexsyn partners with John VanDrie and associates to provide molecular modelling capabilities. The overall aim of CADD is to reduce the number of design-synthesis-test cycles in medicinal chemistry, and to ensure that the maximum is ‘learned’ from each analog.
Each molecular attribute is susceptible to modeling:

for potency,

if an Xray structure of the target is available, structure-based design (SBDD) is used;
if no Xray structure is available, but one is available of a homologous target, a homology model is built, and the techniques of SBDD are applied;
if no structural information is available, empirical models (pharmacophore models, QSAR models) are used to guide the design

for pharmacokinetic parameters,

models of permeability and rough estimates of solubility are used to constrain the molecular evolution to regions of chemical space likely to have acceptable PK characteristics

for off-target effects,

a variety of models are available which detect a molecule’s propensity to hit the hERG channel, CyP’s, etc.

We are not wedded to any specific methodology – we use the tools best suited to the problem, in an integrated way. Our CADD scientists distinguish themselves by deep, practical experience in computer-aided drug discovery, with an average of more than a dozen years experience in Pharma research, with experience in the discovery of clinical candidates.

Examples of VanDrie's modelling efforts:

An inhibitor of Hepatitis C virus protease modeled into the active site of that protease.

A series of agonists of the 5-HT2c receptor overlaid via a pharmacophore, and modeled into the putative binding site.