SlideShare ist ein Scribd-Unternehmen logo
1 von 20
Downloaden Sie, um offline zu lesen
Scaffold Hopping using ONTOMINE TM
Scaffold Hopping: Define ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 
Distribution of 3297 Categorized “High, Medium, Low” Ontomine Hits
Categorized distribution (High, Medium and Low) of 268 active compounds in a Bio-assay with respect to the 4 known NNRTI compounds
Computational ADMET using ONTOMINE TM
Development time and Expense factors in Drug Discovery The attrition rate is unacceptably high. Only 1 out of 12 drugs entering  clinical trials becomes a new drug Lacking appropriate bioavailability, exhibit poor pharmacokinetics or cause  adverse events With the increasing pressure on reducing animal experiments, Computational toxicology and ADME have an increasingly important role to play.  Why ADME-Tox Prediction? Ontomine (vHTS & ADMET)
ADMET Physicochemical Property Prediction Scaffold Hopping Bio Assay Screening Active Compound With Good ADMET Features Ontomine ADMET
[object Object],[object Object],[object Object],[object Object],[object Object],OntoMine ADME predicts physicochemical properties of organic/inorganic  compounds at 25 degree C and neutral pH at present. Ontomine - ADME Predicted Physicochemical Properties Test Mol - Aspirin
Few Example Predictions Aspirin: Well known analgesic drug Experimental Values Ontomine-ADME Prediction Solubility: Soluble Solubility: Soluble (logS=-1.42 LogP: 1.4 LogP: 1.51 Pka: 3.48 Pka: 3.48 Camphor: Chemical used in perfume Experimental values Ontomine-ADME Prediction Solubility: Soluble Solubility: Soluble (logS=-1.42 LogS: -1.98 LogP: 1.51 LogP: 2.38 Pka: 3.48
Few More... Name Exp_logS Pred_logS Exp_logP Pred_logP Exp_pKa Pred_pKa Aspirin -1.59 -1.41 1.19 1.51 3.49 3.45 (Acidic pKa) Camphor -1.98 -2.55 2.38 2.86 No pKa Ciprofloxacin -1.04 -0.46 0.28 0.58 6.09 5.33 (Acidic pKa), 7.7 (Base pKa) Rifampicin -2.77 -3.56 4.24 2.55 6.74 (Acid pKa), 5.65 (Base pKa) Cloroquine -4.48 -5.16 4.63 4.47 10.1 10.1 (Base pKa)
ADME Based Lead Optimization A Case Study - Curcumin
Principal curcuminoid of the popular Indian spice turmeric Induce apoptosis in cancer cells Functional groups characteristic of curcumin scaffold are aromatic ring systems specifically polyphenols that are connected by two α,β-unsaturated carbonyl groups Curcumin – A Case Study Curcumin Water Insoluble Poor Bioavailability Limiting its medicinal use for humans when it is taken orally or injected
Obtaining Curcumin analogues Searching Curcumin – structurally similar molecules in Pubchem retrieves  15697 hits  (Searching Criteria : More than 80% similarity) Finding solubility using Ontomine-ADME Molecules are grouped based on solubility level Highly Soluble – 395 Soluble – 3555 Partially Soluble – 6933 Insoluble – 4813
Curcumin 2D Structural Pattern Solubility Level Confidence Level Ontomine-ADME
Bioactivity Studies on curcumin results  Tissue-nonspecific alkaline phosphatase precursor Inhibitor Analgesics,NonNarcotic Anti-Rheumatic Agents Anti-InflammatoryAgents,NonSteroidal Enzyme Inhibitors Anti-Neoplastic Agents Analogues are explored for Anti-Inflammatory and Anti-Neoplastic activities (Key features of Curcumin)  Analogues are checked for Toxicity using Ontomine-Tox
High Confident Hits with Better ADME Features
Analogue with Priority One Ranking Analogues based on ADME Features, Bioactivity, and Toxicity Mol ID:  16722486 Solubility: Soluble logP: 4.56 Bioactivity: Anti-InflammatoryAgents,NonSteroidal, Anti-Neoplastic Agents Toxicity: No toxicity Predicted Differ from Curcumin: Added two COOH groups SMILE: O=C(O)C=2C=C(C=CC(=O)CC(=O)C=CC=1C=C(OC)C(O)=C(C=1)C(=O)O)C=C(OC)C=2(O)
Thank You

Weitere ähnliche Inhalte

Was ist angesagt? (20)

Continuous flow reaction/ Chemistry
Continuous flow reaction/ ChemistryContinuous flow reaction/ Chemistry
Continuous flow reaction/ Chemistry
 
Prodrug new
Prodrug newProdrug new
Prodrug new
 
Stan Kahler CV 2016
Stan Kahler CV 2016Stan Kahler CV 2016
Stan Kahler CV 2016
 
Pharmacosomes
PharmacosomesPharmacosomes
Pharmacosomes
 
24.prodrug
24.prodrug24.prodrug
24.prodrug
 
Medicinal chemistry
Medicinal chemistryMedicinal chemistry
Medicinal chemistry
 
Mutual prodrugs
Mutual prodrugsMutual prodrugs
Mutual prodrugs
 
Structure based drug design
Structure based drug designStructure based drug design
Structure based drug design
 
J comb chem
J comb chemJ comb chem
J comb chem
 
Prodrug Design
Prodrug DesignProdrug Design
Prodrug Design
 
Reaxys Medicinal Chemistry
Reaxys Medicinal ChemistryReaxys Medicinal Chemistry
Reaxys Medicinal Chemistry
 
Stephen 205 (1)
Stephen 205 (1)Stephen 205 (1)
Stephen 205 (1)
 
Prodrug
ProdrugProdrug
Prodrug
 
Drug excipient interaction
Drug excipient interactionDrug excipient interaction
Drug excipient interaction
 
CLASSIFICATION AND NOMENCLATURE OF DRUGS AND STUBILITY
CLASSIFICATION AND NOMENCLATURE  OF DRUGS AND STUBILITY CLASSIFICATION AND NOMENCLATURE  OF DRUGS AND STUBILITY
CLASSIFICATION AND NOMENCLATURE OF DRUGS AND STUBILITY
 
Prodrugs
ProdrugsProdrugs
Prodrugs
 
Prodrug ramit
Prodrug ramitProdrug ramit
Prodrug ramit
 
Prodrug
ProdrugProdrug
Prodrug
 
Prodrug
ProdrugProdrug
Prodrug
 
Medicinal chemistry
Medicinal chemistryMedicinal chemistry
Medicinal chemistry
 

Andere mochten auch

160929 roche presentation molecule to business
160929 roche presentation molecule to business160929 roche presentation molecule to business
160929 roche presentation molecule to businessSMBBV
 
Software resources in drug design
Software resources in drug designSoftware resources in drug design
Software resources in drug designSurmil Shah
 
Rings In (Candidate) Drugs - Case Stories
Rings In (Candidate) Drugs - Case StoriesRings In (Candidate) Drugs - Case Stories
Rings In (Candidate) Drugs - Case StoriesJonas Boström
 
In silico drug design an intro
In silico drug design   an introIn silico drug design   an intro
In silico drug design an introPrasanthperceptron
 
Superimposition method- ligand based drug design
Superimposition method- ligand based drug designSuperimposition method- ligand based drug design
Superimposition method- ligand based drug designIshpreet Sachdev
 
Structure Based Drug Design
Structure Based Drug DesignStructure Based Drug Design
Structure Based Drug Designdikheidi
 
FiberDock: Flexible Protein Docking with Normal Mode
FiberDock: Flexible Protein Docking with Normal ModeFiberDock: Flexible Protein Docking with Normal Mode
FiberDock: Flexible Protein Docking with Normal ModeMasahito Ohue
 
In Silico Drug Designing
In Silico Drug Designing In Silico Drug Designing
In Silico Drug Designing PALWINDER GILL
 
Biosphere Reserves
Biosphere ReservesBiosphere Reserves
Biosphere ReservesManideep Raj
 
Pharmacohoreppt
PharmacohorepptPharmacohoreppt
PharmacohorepptAbhik Seal
 
presentation on in silico studies
presentation on in silico studiespresentation on in silico studies
presentation on in silico studiesShaik Sana
 
Structure Based Drug Design
Structure Based Drug DesignStructure Based Drug Design
Structure Based Drug Designnmicaelo
 
biosphere Case
biosphere Casebiosphere Case
biosphere Caserajnikant
 
STRUCTURE BASED DRUG DESIGN - MOLECULAR MODELLING AND DRUG DISCOVERY
STRUCTURE BASED DRUG DESIGN - MOLECULAR MODELLING AND DRUG DISCOVERYSTRUCTURE BASED DRUG DESIGN - MOLECULAR MODELLING AND DRUG DISCOVERY
STRUCTURE BASED DRUG DESIGN - MOLECULAR MODELLING AND DRUG DISCOVERYTHILAKAR MANI
 
Structure based drug design
Structure based drug designStructure based drug design
Structure based drug designADAM S
 
1 -val_gillet_-_ligand-based_and_structure-based_virtual_screening
1  -val_gillet_-_ligand-based_and_structure-based_virtual_screening1  -val_gillet_-_ligand-based_and_structure-based_virtual_screening
1 -val_gillet_-_ligand-based_and_structure-based_virtual_screeningDeependra Ban
 
Renewable And Non Renewable Sources Of Energy
Renewable And Non Renewable Sources Of EnergyRenewable And Non Renewable Sources Of Energy
Renewable And Non Renewable Sources Of Energyoneworld.abhiraj
 

Andere mochten auch (20)

160929 roche presentation molecule to business
160929 roche presentation molecule to business160929 roche presentation molecule to business
160929 roche presentation molecule to business
 
project presentation
project presentationproject presentation
project presentation
 
Software resources in drug design
Software resources in drug designSoftware resources in drug design
Software resources in drug design
 
Rings In (Candidate) Drugs - Case Stories
Rings In (Candidate) Drugs - Case StoriesRings In (Candidate) Drugs - Case Stories
Rings In (Candidate) Drugs - Case Stories
 
In silico drug design an intro
In silico drug design   an introIn silico drug design   an intro
In silico drug design an intro
 
Superimposition method- ligand based drug design
Superimposition method- ligand based drug designSuperimposition method- ligand based drug design
Superimposition method- ligand based drug design
 
Structure Based Drug Design
Structure Based Drug DesignStructure Based Drug Design
Structure Based Drug Design
 
FiberDock: Flexible Protein Docking with Normal Mode
FiberDock: Flexible Protein Docking with Normal ModeFiberDock: Flexible Protein Docking with Normal Mode
FiberDock: Flexible Protein Docking with Normal Mode
 
In Silico Drug Designing
In Silico Drug Designing In Silico Drug Designing
In Silico Drug Designing
 
Biosphere Reserves
Biosphere ReservesBiosphere Reserves
Biosphere Reserves
 
Pharmacohoreppt
PharmacohorepptPharmacohoreppt
Pharmacohoreppt
 
presentation on in silico studies
presentation on in silico studiespresentation on in silico studies
presentation on in silico studies
 
Structure Based Drug Design
Structure Based Drug DesignStructure Based Drug Design
Structure Based Drug Design
 
biosphere Case
biosphere Casebiosphere Case
biosphere Case
 
Protein docking
Protein dockingProtein docking
Protein docking
 
Drug design
Drug designDrug design
Drug design
 
STRUCTURE BASED DRUG DESIGN - MOLECULAR MODELLING AND DRUG DISCOVERY
STRUCTURE BASED DRUG DESIGN - MOLECULAR MODELLING AND DRUG DISCOVERYSTRUCTURE BASED DRUG DESIGN - MOLECULAR MODELLING AND DRUG DISCOVERY
STRUCTURE BASED DRUG DESIGN - MOLECULAR MODELLING AND DRUG DISCOVERY
 
Structure based drug design
Structure based drug designStructure based drug design
Structure based drug design
 
1 -val_gillet_-_ligand-based_and_structure-based_virtual_screening
1  -val_gillet_-_ligand-based_and_structure-based_virtual_screening1  -val_gillet_-_ligand-based_and_structure-based_virtual_screening
1 -val_gillet_-_ligand-based_and_structure-based_virtual_screening
 
Renewable And Non Renewable Sources Of Energy
Renewable And Non Renewable Sources Of EnergyRenewable And Non Renewable Sources Of Energy
Renewable And Non Renewable Sources Of Energy
 

Ähnlich wie Ontomine Scaffold Hop

Session 1 part 2
Session 1 part 2Session 1 part 2
Session 1 part 2plmiami
 
First dose size in humans and non linear pharmacokinetics.pptx
First dose size in humans and non linear pharmacokinetics.pptxFirst dose size in humans and non linear pharmacokinetics.pptx
First dose size in humans and non linear pharmacokinetics.pptxABDULRAUF411
 
Drug Discovery Process by Kashikant Yadav
Drug Discovery Process by Kashikant YadavDrug Discovery Process by Kashikant Yadav
Drug Discovery Process by Kashikant YadavKashikant Yadav
 
Drug discovery and development
Drug discovery and developmentDrug discovery and development
Drug discovery and developmentSharafudheenKa4
 
In silico lead discovery technique.pptx
In silico lead discovery technique.pptxIn silico lead discovery technique.pptx
In silico lead discovery technique.pptxSIRAJUDDIN MOLLA
 
Enabling Cancer Immunotherapy: From Discovery to Combinations
Enabling Cancer Immunotherapy: From Discovery to CombinationsEnabling Cancer Immunotherapy: From Discovery to Combinations
Enabling Cancer Immunotherapy: From Discovery to CombinationsDiscoverX Corporation
 
Bioinformatics t9-t10-biocheminformatics v2014
Bioinformatics t9-t10-biocheminformatics v2014Bioinformatics t9-t10-biocheminformatics v2014
Bioinformatics t9-t10-biocheminformatics v2014Prof. Wim Van Criekinge
 
Bioinformatica 15-12-2011-t9-t10-bio cheminformatics
Bioinformatica 15-12-2011-t9-t10-bio cheminformaticsBioinformatica 15-12-2011-t9-t10-bio cheminformatics
Bioinformatica 15-12-2011-t9-t10-bio cheminformaticsProf. Wim Van Criekinge
 
Session 1 part 3
Session 1 part 3Session 1 part 3
Session 1 part 3plmiami
 
Biopharmaceutical Classification System
Biopharmaceutical Classification SystemBiopharmaceutical Classification System
Biopharmaceutical Classification SystemSHATRUGHAN CHAUDHARY
 
Bioequivalence
BioequivalenceBioequivalence
BioequivalenceGaurav Kr
 
Bioequivalence
BioequivalenceBioequivalence
BioequivalenceGaurav Kr
 
Acute and chronic toxicity studies in animals
Acute and chronic toxicity studies in animalsAcute and chronic toxicity studies in animals
Acute and chronic toxicity studies in animalsSwaroopaNallabariki
 
Pyrogen and its various test
Pyrogen and its various testPyrogen and its various test
Pyrogen and its various testPrachi Barbhaiya
 
Formulation and evaluation of sustained release microspheres of
Formulation and evaluation of sustained release microspheres ofFormulation and evaluation of sustained release microspheres of
Formulation and evaluation of sustained release microspheres ofReshma Fathima .K
 

Ähnlich wie Ontomine Scaffold Hop (20)

Session 1 part 2
Session 1 part 2Session 1 part 2
Session 1 part 2
 
First dose size in humans and non linear pharmacokinetics.pptx
First dose size in humans and non linear pharmacokinetics.pptxFirst dose size in humans and non linear pharmacokinetics.pptx
First dose size in humans and non linear pharmacokinetics.pptx
 
Drug development
Drug developmentDrug development
Drug development
 
Opensourcepharma Dr Nibedita rath
Opensourcepharma Dr Nibedita rathOpensourcepharma Dr Nibedita rath
Opensourcepharma Dr Nibedita rath
 
Drug Discovery Process by Kashikant Yadav
Drug Discovery Process by Kashikant YadavDrug Discovery Process by Kashikant Yadav
Drug Discovery Process by Kashikant Yadav
 
Drug discovery and development
Drug discovery and developmentDrug discovery and development
Drug discovery and development
 
In silico lead discovery technique.pptx
In silico lead discovery technique.pptxIn silico lead discovery technique.pptx
In silico lead discovery technique.pptx
 
Workplace Drug Screening Using Liquid Chromatography-Tandem Mass Spectrometry...
Workplace Drug Screening Using Liquid Chromatography-Tandem Mass Spectrometry...Workplace Drug Screening Using Liquid Chromatography-Tandem Mass Spectrometry...
Workplace Drug Screening Using Liquid Chromatography-Tandem Mass Spectrometry...
 
Enabling Cancer Immunotherapy: From Discovery to Combinations
Enabling Cancer Immunotherapy: From Discovery to CombinationsEnabling Cancer Immunotherapy: From Discovery to Combinations
Enabling Cancer Immunotherapy: From Discovery to Combinations
 
Bioinformatics t9-t10-biocheminformatics v2014
Bioinformatics t9-t10-biocheminformatics v2014Bioinformatics t9-t10-biocheminformatics v2014
Bioinformatics t9-t10-biocheminformatics v2014
 
drug discovery.pptx
drug discovery.pptxdrug discovery.pptx
drug discovery.pptx
 
Bioinformatica 15-12-2011-t9-t10-bio cheminformatics
Bioinformatica 15-12-2011-t9-t10-bio cheminformaticsBioinformatica 15-12-2011-t9-t10-bio cheminformatics
Bioinformatica 15-12-2011-t9-t10-bio cheminformatics
 
Session 1 part 3
Session 1 part 3Session 1 part 3
Session 1 part 3
 
Biopharmaceutical Classification System
Biopharmaceutical Classification SystemBiopharmaceutical Classification System
Biopharmaceutical Classification System
 
Biopharmaceutical shatrughan
Biopharmaceutical shatrughanBiopharmaceutical shatrughan
Biopharmaceutical shatrughan
 
Bioequivalence
BioequivalenceBioequivalence
Bioequivalence
 
Bioequivalence
BioequivalenceBioequivalence
Bioequivalence
 
Acute and chronic toxicity studies in animals
Acute and chronic toxicity studies in animalsAcute and chronic toxicity studies in animals
Acute and chronic toxicity studies in animals
 
Pyrogen and its various test
Pyrogen and its various testPyrogen and its various test
Pyrogen and its various test
 
Formulation and evaluation of sustained release microspheres of
Formulation and evaluation of sustained release microspheres ofFormulation and evaluation of sustained release microspheres of
Formulation and evaluation of sustained release microspheres of
 

Ontomine Scaffold Hop

  • 2.
  • 3.
  • 4.  
  • 5. Distribution of 3297 Categorized “High, Medium, Low” Ontomine Hits
  • 6. Categorized distribution (High, Medium and Low) of 268 active compounds in a Bio-assay with respect to the 4 known NNRTI compounds
  • 8. Development time and Expense factors in Drug Discovery The attrition rate is unacceptably high. Only 1 out of 12 drugs entering clinical trials becomes a new drug Lacking appropriate bioavailability, exhibit poor pharmacokinetics or cause adverse events With the increasing pressure on reducing animal experiments, Computational toxicology and ADME have an increasingly important role to play. Why ADME-Tox Prediction? Ontomine (vHTS & ADMET)
  • 9. ADMET Physicochemical Property Prediction Scaffold Hopping Bio Assay Screening Active Compound With Good ADMET Features Ontomine ADMET
  • 10.
  • 11. Few Example Predictions Aspirin: Well known analgesic drug Experimental Values Ontomine-ADME Prediction Solubility: Soluble Solubility: Soluble (logS=-1.42 LogP: 1.4 LogP: 1.51 Pka: 3.48 Pka: 3.48 Camphor: Chemical used in perfume Experimental values Ontomine-ADME Prediction Solubility: Soluble Solubility: Soluble (logS=-1.42 LogS: -1.98 LogP: 1.51 LogP: 2.38 Pka: 3.48
  • 12. Few More... Name Exp_logS Pred_logS Exp_logP Pred_logP Exp_pKa Pred_pKa Aspirin -1.59 -1.41 1.19 1.51 3.49 3.45 (Acidic pKa) Camphor -1.98 -2.55 2.38 2.86 No pKa Ciprofloxacin -1.04 -0.46 0.28 0.58 6.09 5.33 (Acidic pKa), 7.7 (Base pKa) Rifampicin -2.77 -3.56 4.24 2.55 6.74 (Acid pKa), 5.65 (Base pKa) Cloroquine -4.48 -5.16 4.63 4.47 10.1 10.1 (Base pKa)
  • 13. ADME Based Lead Optimization A Case Study - Curcumin
  • 14. Principal curcuminoid of the popular Indian spice turmeric Induce apoptosis in cancer cells Functional groups characteristic of curcumin scaffold are aromatic ring systems specifically polyphenols that are connected by two α,β-unsaturated carbonyl groups Curcumin – A Case Study Curcumin Water Insoluble Poor Bioavailability Limiting its medicinal use for humans when it is taken orally or injected
  • 15. Obtaining Curcumin analogues Searching Curcumin – structurally similar molecules in Pubchem retrieves 15697 hits (Searching Criteria : More than 80% similarity) Finding solubility using Ontomine-ADME Molecules are grouped based on solubility level Highly Soluble – 395 Soluble – 3555 Partially Soluble – 6933 Insoluble – 4813
  • 16. Curcumin 2D Structural Pattern Solubility Level Confidence Level Ontomine-ADME
  • 17. Bioactivity Studies on curcumin results Tissue-nonspecific alkaline phosphatase precursor Inhibitor Analgesics,NonNarcotic Anti-Rheumatic Agents Anti-InflammatoryAgents,NonSteroidal Enzyme Inhibitors Anti-Neoplastic Agents Analogues are explored for Anti-Inflammatory and Anti-Neoplastic activities (Key features of Curcumin) Analogues are checked for Toxicity using Ontomine-Tox
  • 18. High Confident Hits with Better ADME Features
  • 19. Analogue with Priority One Ranking Analogues based on ADME Features, Bioactivity, and Toxicity Mol ID: 16722486 Solubility: Soluble logP: 4.56 Bioactivity: Anti-InflammatoryAgents,NonSteroidal, Anti-Neoplastic Agents Toxicity: No toxicity Predicted Differ from Curcumin: Added two COOH groups SMILE: O=C(O)C=2C=C(C=CC(=O)CC(=O)C=CC=1C=C(OC)C(O)=C(C=1)C(=O)O)C=C(OC)C=2(O)