ProtoScreen™

ProtoScreen™ is a robust virtual screening application developed as part as ProtoDiscovery™ software platform.

ProtoScreen™ is a multiconfomer docking program in which confomers are fitted to an active site using a Gaussian scoring function. Poses are then optimised and scored in the context of the ProtoScore™ predictive affinity function. Pre-computed confomers in the ProtoDiscovery™ Compound Database [PCD] enable a rapid screening rate of seconds per compound.

ProtoScreen™ has been subjected to extensive biological validation with excellent hit rates and enrichments determined for many targets.

ProtoScreen™ has been used successfully to identify novel ligands for many targets including a number of GPCRs, for both in-house and partner driven projects. The following tables show relevant in vitro results for some ProtoScreen™ campaigns

Enzyme and Nuclear Receptor Targets
Program In silico screen size[1] No. of compounds tested No. of hits (inhibition @10µM) Best hit(% inhibition) Hit rate Best hit Ki (nM) Novelty[2]
[1] Size of PCD at time of screening;
[2] % of novel hits based on SciFinder® searches
Enzyme Target 1 ~1.2 M 43 24 75% 52% 3100 87%
Nuclear Receptor ~1.2 M 51 17 100% 33% 490 100%
Enzyme Target 2 2.5 M 31 6 100% 19% 5500 84%
Enzyme Target 3 3 M 140 14 100% 10% 88 100%
Enzyme Target 4 3M 30 2 80% 7% 6000 100%

ProtoScreen™ has also been applied systematically to five GPCR models. From the resulting in vitro data and activity profiles novel hits have been obtained which have been used as the basis for subsequent medicinal chemistry programs.

GPCR Targets
Program In silico screen size[1] No. of compounds tested No. of hits (inhibition @10µM) Best hit(% inhibition) Hit rate Best hit Ki (nM) Novelty[2]
[1] Size of PCD at time of screening;
[2] % of novel hits based on SciFinder® searches
Target 1 agonist ~2.5 M 51 37 100% 65% 5 65%
Target 2 agonist ~3 M 88 18 77% 20% 5500 100%
Target 3 antagonist ~3 M 67 8 100% 12% 2500 75%
Target 4 antagonist ~3 M 11 5 98% 45% 90 100%
Target 5 agonist ~3M 28 8 100% 29% tbc 100%

Prosarix offer ProtoScreen™ as a service for structure based design projects.

 

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