The core of ARK™ is an automatic feedback loop that supports medicinal chemists with information for prioritization and optimization of libraries and lead compounds. While exploring ideas in ARK™, virtual molecules are entered into the database and molecular descriptors (physicochemical properties, ADME, toxicity) are calculated and the predicted potency and selectivity for the selected target are immediately sent to the chemist. Eidogen-Sertanty uses an enhanced, proprietary 3-point-pharmacophore fingerprint technology and high quality empirical SAR data to develop target specific eScreen results against a single target or an entire gene family.

Avoid failure of compounds in the clinic by designing a desirable selectivity profile. Very few compounds are tested for selectivity in the early lead discovery stage because biological screening of a large number of compounds against an entire panel of targets is not financially feasible. As a result, the "selectivity matrix" of randomly picked example kinase inhibitors below (Figure 1) is grey.

Figure 1.  Experimental IC50 data

Eidogen-Sertanty's eScreen® technology represents a cost effective in silico method to check literally millions of virtual molecules for potency and selectivity. "Hot Spots" in the selectivity matrix alert researchers early on to select and monitor anti-targets and therefore reduce failure rates in the clinic (Figure 2).

Figure 2.  eScreen enriched pIC50 data

The eScreen® process enables scaffold jumping as well as lead optimization. Eidogen-Sertanty works closely with its clients to assure that training sets and models are optimized for the individual research project.

The following eScreen® models are currently available for the kinase family:

AGC Kinase Models PKA PKC PRKCA PRKCB1 PRKCD PRKCA_DAG PRKCB1_DAG PRKCE_DAG PRKCG_DAG PRKCH_DAG PDK CMGC Kinase Models CDC2 CDK1_B CDK2 CDK2_A CDK2_E CDK4_D1 CDK4_D2 CDK5 CDK5_P25 CDK5_P35 MAPK14 GSK3A GSK3B

Receptor Tyrosine Kinase Models CSK SRC FYN LCK ABL SYK ZAP_70_SH2 GRB2_SH2 EGFR ERBB2 FGFR EGFR_SUBSTRATE PDGFR PDGFRB FLT1 KDR TEK TKL and STE Kinase Models RAF1 MAP2K Others ADK PPK PIK4CA

Data Access

The eScreen® training sets can be purchased in SD or TDT file format.