Aurigene’s Integrated Research Model is the core strength that has enabled Aurigene to build an exemplary track-record for managing and delivering successful candidates on its own and to its partners. Specific case-studies exemplifying Aurigene’s ability to successfully solve discovery challenges are highlighted in the links below.

Genetic Validation


  • Transfection of siRNA for the target of interest (T= targeting) resulted in reduction in target protein levels as determined by Western blot analysis (Panel A) that correlated well with inhibition of substrate modulation in a biochemical assay (Panel B) and inhibition of NSCLC cell proliferation (Panel C).

Pharmacological Validation


  • Studies with a selective small molecule inhibitor indicated significant reduction of proliferation of cancer cells but not normal cells (Panel A).
  • Sensitivity of breast cancer cells correlated with the expression of a helper protein, which could potentially be used a predictive biomarker (Panel B).

Early Efficacy and Toxicity Evaluation

  • Comparison of the doses required to achieve efficient tumor growth inhibition (TGI) and that shows good tolerability in repeated dose studies indicated an acceptable therapeutic window.

Validation summary

  • Based on the findings in target validation studies, this target was selected for a fully resourced drug discovery program.
Screen Shot 2015-12-16 at 2.52.02 PM
  • Based on literature crystal structure of matriptase catalytic domain in complex with benzamidine sulfate, we hypothesized that benzamidine could engage sulfate pocket & spacious solvent exposed S3/S4 region.
  • Few focused libraries were designed and screened.
  • The initial hits were further refined through series of co-crystal structure and modeling analysis (SBDD) to get potent hit (Ki = 40nM).
  • The hit had favorable selectivity over undesirable serine proteases, besides desired cellular activity, solubility, and metabolic stability.

Ref: ACS Med. Chem. Lett. 2013, 4, 1152−1157

Screen Shot 2015-12-16 at 2.54.55 PM

  • Compound-1 was a potent ALK inhibitor (WT and mutant), with undesired inhibition of Aurora A kinase activity (implicated in cardio toxicity).
  • From SBDD analysis, it was found proximity of pyrazole N2 nitrogen to catalytic Lys-162 of Aurora A (3Å distance) compared to ALK (4.4Å distance), was responsible for lack of selectivity.
  • Disrupting the above interaction by having dimethyl pyrazole in compound-2, resulted in greater selectivity for Aurora A.

Ref: Bioorg. Med. Chem. Lett., 2013, 23, 4911

Screen Shot 2015-12-16 at 2.59.59 PM

  • The high efflux ratio of compound-1 was reduced by
    • H-bond donor capacity reduced by changing from primary amide (1) to secondary amide (2)
    • Decreasing H-bond acceptor potential (oxetane replaced with azetidine)
  • The attenuation of efflux in compound-2 resulted in improved gastrointestinal absorption and bioavailability (>30 %F).