Make the right decisionswith data youcan trust<br />
Instructionsforattendees<br />The webinar hasn’t started yet. It will start at 5:05 pm when allattendees are connected. T...
Prediction of Adverse Drug ReactionsMediated by Off-TargetsUsing AurPASS<br />
Safety and  Adverse Effects<br />Every year about 2 million patients in the United States are affected by a serious advers...
What is an off-target or anti-target?<br />Off-Targets and Preclinical Safety Pharmacology<br />Case Studies of Drug Failu...
Aureus at a Glance<br />Aureus is a knowledge and information management solutions provider for the Life Science industry ...
Aureus 10 YearsExperience of Building SAR Databases<br />6/30/2011<br />7<br />AurPASS<br />
AurSCOPE  Knowledge Databases Target Pharmacological Space<br />2002<br />2004<br />2005<br />2008<br />2009<br />Nuclear ...
AurSCOPE Knowledge Databases ADME/DDI & TOX<br />Off-Targets<br />ADME/DDI<br />12,165 including<br />200 FDA Reviews<br /...
AurSCOPE GPS : Global Pharmacological Database<br />2009<br />2010<br />2011<br />GPCR<br />Ion<br />Channel<br />Kinase<b...
Make The Right Decision With Data You Can Trust<br />AurPROFILER<br />Data analysis & Navigation<br />Medicinal Chemistry ...
Filling the Gap Using AurPASS in silicoPredictions<br />12<br />Aureus<br />Prediction of<br />Activity<br />Spectra for<b...
Predicting New Activities on Selectedbig Pharma Drugs<br />Off-Targets<br />SelectedMoleculesfrom Pharma Pipeline<br />13<...
Over Forty Publications with Independent Confirmation of PASS Predictions…<br />14<br />AurPASS<br />More References in au...
		AurPASS<br />Training Set<br />SAR data extracted from individual AurSCOPE databases<br />Chemical & biological post-pro...
			AurPASS Off-Target Modules<br />16<br />Live Demo<br />AurPASS<br />
AurPASS<br />Training Set<br />SAR data extracted from individual AurSCOPEknowledgebases<br />Chemical & biological post-p...
Selected Off-Targets and AssociatedADRs<br />6/30/2011<br />18<br />SAR information for these targets can be displayed in ...
	Content Description of Aureus Knowledgebases….<br />6/30/2011<br />19<br />AurPASS<br />
	Added Value of Aureus Data for Predictive Models<br />20<br />ChemicalProcessing<br /><ul><li> No Peptides
 No mixtures
Inorganic and metalo-organicremoval
 Charge standardization</li></ul>BiologicalProcessing<br />hERG Channel<br /><ul><li>Biologicalprotocols
Target hierarchy
Target species, celllinesand tissues
Biologicalactivityparameters
Ligand action on target</li></ul>AurPASS<br />
21<br />6/30/2011<br />	Added Value of Aureus Data for Predictive Models<br />AssigningActivity Classes<br />Actives & Ina...
	Encoding Chemical Structures: MNA Descriptors<br />22<br />	MNA/2<br />C(C(CC-H)C(CC-C)-H(C))<br />C(C(CC-H)C(CN-H)-H(C))...
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Webinar : AurPASS Off-Targets

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Webinar : AurPASS Off-Targets

  1. 1. Make the right decisionswith data youcan trust<br />
  2. 2. Instructionsforattendees<br />The webinar hasn’t started yet. It will start at 5:05 pm when allattendees are connected. Thank you for your patience.<br /> To connect to the audio conference, please go to the top menu and click on Communicate>Teleconference>Join Teleconference and select the phone number to call.<br />Before starting <br />We will mute your microphone during the webinar<br />During the webinar<br />Use the chat for questions<br />At the End <br />You can ask your questions orally<br />We will answer them either in the webinar session or later on by email.<br />2<br />AurPASS<br />
  3. 3. Prediction of Adverse Drug ReactionsMediated by Off-TargetsUsing AurPASS<br />
  4. 4. Safety and Adverse Effects<br />Every year about 2 million patients in the United States are affected by a serious adverse drug reaction. <br />This results in approximately 100,000 fatalities, making ADRs the fourth leading cause of death in the U.S. <br />The consequence is a huge burden on national economies, which is estimated to be $136 billion annually in the U.S. <br />Over the past 10 years, 19 broadly used marketed drugs were withdrawn after presenting unexpected severe side effects, with Rofecoxib and Cerivastatin.<br />30/06/2011<br />4<br />AurPASS<br />
  5. 5. What is an off-target or anti-target?<br />Off-Targets and Preclinical Safety Pharmacology<br />Case Studies of Drug Failures Related to Off-Target Activities<br />Off-Targets in Gene Families <br />Ion Channels<br />GPCRs<br />Nuclear Receptors<br />Cytochrome P450<br />Transporters<br />Delimiting the Chemical Space of Off-Targets<br />Predicting Off-Targets<br /> Off-Targets in Gene Families<br />5<br />AurPASS<br />
  6. 6. Aureus at a Glance<br />Aureus is a knowledge and information management solutions provider for the Life Science industry located in Paris. <br />Over the past 10 years the company has developed a unique knowledge production platform which stores, indexes and organizes critical chemical and bioactivity information including experimental in vitro and in vivo protocols from the public or private literature.<br />Aureus employees 20 highlevelscientists (PhD and MSc) includingscientific and IT project leaders and documentation analysts<br />Aureus is funded by institutional investors like CDC Entreprise, AXA Provate Equity, OTC Asset Management and is part of the OSEO Excellence innovation team.<br />07/04/2011<br />6<br />AurPASS<br />
  7. 7. Aureus 10 YearsExperience of Building SAR Databases<br />6/30/2011<br />7<br />AurPASS<br />
  8. 8. AurSCOPE Knowledge Databases Target Pharmacological Space<br />2002<br />2004<br />2005<br />2008<br />2009<br />Nuclear Receptor<br />Protease<br />GPCR<br />Kinase<br />Ion Channel<br /> 13,303 including <br /> 6,966 patents<br />32,588 including <br />15,281 patents<br />4,668 including<br />2,484 patents<br />4,226 including<br />1,060 patents<br />10,206 including <br />6,806 patents<br />Publications<br />Biological<br />Activities<br />275,044<br />418,202<br />186,047<br />1,243,793<br />670,407<br />98,439<br />354,323<br />146,426<br />Unique <br />Ligands<br />124,313<br />48,500<br />Biological<br />Protocols<br />8<br />AurPASS<br />
  9. 9. AurSCOPE Knowledge Databases ADME/DDI & TOX<br />Off-Targets<br />ADME/DDI<br />12,165 including<br />200 FDA Reviews<br />10,700<br />Publications<br />315,200<br />462,785<br />Biological<br />Activities<br />Unique <br />Ligands<br />34,872 compounds <br />including 4,050 metabolites<br />Biological<br />Protocols<br />9<br />AurPASS<br />107,646 compounds <br />
  10. 10. AurSCOPE GPS : Global Pharmacological Database<br />2009<br />2010<br />2011<br />GPCR<br />Ion<br />Channel<br />Kinase<br />NHR<br />Protease<br />ADME<br />Off Targets<br />30/06/2011<br />10<br />AurPASS<br />
  11. 11. Make The Right Decision With Data You Can Trust<br />AurPROFILER<br />Data analysis & Navigation<br />Medicinal Chemistry Space<br />AurQUEST<br />Data mining<br />AurPASS<br />Predict Biological <br />Activities Spectra<br />DDI Predict<br />AurPASS<br />11<br />
  12. 12. Filling the Gap Using AurPASS in silicoPredictions<br />12<br />Aureus<br />Prediction of<br />Activity<br />Spectra for<br />Substances<br />AurPASS<br />ADME<br />Off Targets<br />GPCR<br />Ion<br />Channel<br />Kinase<br />NHR<br />Protease<br />
  13. 13. Predicting New Activities on Selectedbig Pharma Drugs<br />Off-Targets<br />SelectedMoleculesfrom Pharma Pipeline<br />13<br />AurPASS<br />
  14. 14. Over Forty Publications with Independent Confirmation of PASS Predictions…<br />14<br />AurPASS<br />More References in aureus-sciences.com/ResourceCenter<br />
  15. 15. AurPASS<br />Training Set<br />SAR data extracted from individual AurSCOPE databases<br />Chemical & biological post-processing<br />Chemical Structures<br />Multilevel Neighborhoods of Atoms (MNA) descriptors<br />SAR Base<br />Diverse chemical structures and associated MNA descriptors<br />Associated qualitative biologicalactivity types<br />Prediction Algorithm<br />PASS Bayesian approach<br />Models Validation<br />LOO and L20%O validations<br />External dataset<br />15<br />AurPASS<br />
  16. 16. AurPASS Off-Target Modules<br />16<br />Live Demo<br />AurPASS<br />
  17. 17. AurPASS<br />Training Set<br />SAR data extracted from individual AurSCOPEknowledgebases<br />Chemical & biological post-processing<br />Chemical Structures<br />Multilevel Neighborhoods of Atoms (MNA) descriptors<br />SAR Base<br />Diverse chemical structures and associated MNA descriptors<br />Associated qualitative biologicalactivity types<br />Prediction Algorithm<br />PASS Bayesian approach<br />Models Validation<br />LOO and L20%O validations<br />External dataset<br />17<br />AurPASS<br />
  18. 18. Selected Off-Targets and AssociatedADRs<br />6/30/2011<br />18<br />SAR information for these targets can be displayed in our portal aureus-sciences.com <br />AurPASS<br />
  19. 19. Content Description of Aureus Knowledgebases….<br />6/30/2011<br />19<br />AurPASS<br />
  20. 20. Added Value of Aureus Data for Predictive Models<br />20<br />ChemicalProcessing<br /><ul><li> No Peptides
  21. 21. No mixtures
  22. 22. Inorganic and metalo-organicremoval
  23. 23. Charge standardization</li></ul>BiologicalProcessing<br />hERG Channel<br /><ul><li>Biologicalprotocols
  24. 24. Target hierarchy
  25. 25. Target species, celllinesand tissues
  26. 26. Biologicalactivityparameters
  27. 27. Ligand action on target</li></ul>AurPASS<br />
  28. 28. 21<br />6/30/2011<br /> Added Value of Aureus Data for Predictive Models<br />AssigningActivity Classes<br />Actives & Inactives<br />Molecules &<br />SAR Data<br />AurPASSActivity Types<br />Actives & Inactives<br />PASS<br />Training/Test Sets<br />AurPASS<br />
  29. 29. Encoding Chemical Structures: MNA Descriptors<br />22<br /> MNA/2<br />C(C(CC-H)C(CC-C)-H(C))<br />C(C(CC-H)C(CN-H)-H(C))<br />C(C(CC-H)C(CN-H)-C(C-O-O))<br />C(C(CC-H)N(CC)-H(C))<br />C(C(CC-C)N(CC)-H(C))<br />N(C(CN-H)C(CN-H))<br />-H(C(CC-H))<br />-H(C(CN-H))<br />-H(-O(-H-C))<br />-C(C(CC-C)-O(-H-C)-O(-C))<br />-O(-H(-O)-C(C-O-O))<br />-O(-C(C-O-O))<br />MNA/0: C<br />AurPASS<br />MNA/1: C(CN-H)<br />MNA/2: C(C(CC-H)N(CC)-H(C))<br />
  30. 30. PASS Approach for Biological Activity Prediction<br />Predicted values are “Probability Estimations”<br />In all AurPASS modules, “Actives” are defined by a biological threshold less than 10 µM. <br />The list of activities which are probable for a particular compound with the estimates for each activity of :<br />Pa: probability to be active<br />Pi: probability to be inactive<br />Pa and Pi are calculated independently: Pa + Pi  1<br />Pa (Pi) can be considered as the probability of the compound belonging to classes of active (inactive) compounds<br />23<br />AurPASS<br />
  31. 31. Internal Validation of AurPASS Off-Target Models<br />AurPASS<br />
  32. 32. AurSCOPE Databases are QuarterlyUpdated (4 releases/Year)<br />Improvement of dataset over time in terms of diversity<br />Updating/Testinggeneratedmodelswith new data<br /> External Validation of AurPASS Off-Targets Models<br />25<br />AurPASS<br />Training Set<br />Release n-1<br />Test Set<br />Release n<br />3 monthslater<br />AurPASS Ion Channels<br />47 938 Molecules<br />517 Activity Types <br />Mean Accuracy of Prediction: 98% <br />2 244 new Molecules<br />113 Activity Types <br />Mean Accuracy of Prediction: 90% <br />
  33. 33. 6/30/2011<br />26<br />Can be downloaded from aureus-sciences.com/ResourceCenter<br />
  34. 34. AurPASS Off-Target <br /> …is a desktop application licensed on a user basis.<br /> It contains the Aureus Off-Target dataset model. <br />Off-Target Database<br />…is the completedatabase accessible through the Aureus Web Portal and licensed on an annualsubscription mode<br />AurPASS Product Line Aureus On Line Databases<br />AurPASS Ion Channel Ion Channel 365 Targets / 130 000 Molecules<br />AurPASS Kinase Kinase 1010 Targets / 190 000 Molecules<br />AurpASS GPCR GPCR 555 Targets / 380 000 Molecules<br />AurPASS Off Target Off Target 70 Targets / 107 000 Molecules<br />27<br />AurPASSOffers<br />AurPASS<br />
  35. 35. 28<br /> For More Information<br />Aureus Sciences<br />www.aureus-sciences.com<br />contact@aureus-sciences.com<br />Tel: +33 1 40 18 57 57<br />Or Aureus Distributors<br />AKOS (Germany) www.akosgmbh.de<br />AriadneGenomics (U.S.) www.ariadnegenomics.com<br />Patcore (Japan) www.patcore.com<br />Pharmogo (China) www.pharmogo.com<br />AurPASS<br />
  36. 36. Thank you for your attention<br />174, Quai de Jemmapes <br />75010 Paris, FRANCE<br />www.aureus-sciences.com<br />29<br />

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