These are the slides for the Reaxys Medicinal Chemistry webinar that was held on October 16, 2013.

1. INTRODUCTION TO
REAXYS MEDICINAL CHEMISTRY
Webinar presented October 16, 2013
Olivier Barberan
Senior Product Manager
Your Presenter: Dr. Olivier Barberan
Elsevier
October 16, 2013
1

2. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER
SITUATION: DRUG DISCOVERY
ELN
Known ligands
Knowledge
survey
Therapeutic
target
Chemistry
Generate
chemistry ideas
DBs
Check chemical
feasibility
In-house
Analyze
SAR
Synthesize
or buy
Report
Test
Check
No single solution will fit all
ADME/Tox
needs, but…
Journals
ELN
Biology
Docs
Flatfiles
Journals
2

3. In-house
Known ligands
Knowledge
survey
Therapeutic
target
Generate
chemistry ideas
Analyze
SAR
Report
Chemistry
Check chemical
feasibility
Synthesize
or buy
Test
… is that really being able
Wouldn’t it be nicenecessary? to
Check
switch seamlessly between scientific
ADME/Tox
Hows about interoperability and
domains andintegration?
find data that you have
Biology
not even thought about, but would
be important?
Docs
3
Flatfiles
ELN

4. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER
AGENDA
Elsevier Life science Solution
Reaxys Medicinal Chemistry
Content coverage
Application in Drug discovery
QA
4

5. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER
PART OF LIFE SCIENCE SOLUTIONS
A SUITE OF INTEROPERABLE, DOMAIN-SPECIFIC, DECISION SUPPORT TOOLS
MEDSCAN
TEXT MINING
TARGETINSIGHTS
(CONTENT)
INTEGRATION
PATHWAY STUDIO
PHARMAPENDIUM
EMBASE
TAXONOMIES
QUOSA
5

6. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER
PART OF LIFE SCIENCE SOLUTIONS
A SUITE OF INTEROPERABLE, DOMAIN-SPECIFIC, DECISION SUPPORT TOOLS
MEDSCAN
REAXYS CHEMISTRY DISCOVERY ENGINE
REAXYS MEDICINAL CHEMISTRY
Combines relevant chemistry information
from 16,000 periodicals and over 500m
TARGETINSIGHTS
experimentally validated facts with
synthesis planning functionality.
Identify, optimize and prioritize
compounds with optimum
PATHWAY STUDIO
affinity, selectivity and ADMET
properties.
(CONTENT)
INTEGRATION
PHARMAPENDIUM
EMBASE
TAXONOMIES
QUOSA
6

7. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER
CONTENT COVERAGE
7

8. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER
ESSENTIAL INFORMATION: 100+ EXPERIMENTAL FIELDS
Reaxys Medicinal Chemistry excerpts all the relevant Quantitative data

9. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER
9
ESSENTIAL INFORMATION: SUPPORTING CRITICAL STAGES
IN THE DRUG DISCOVERY & DEVELOPMENT PIPELINE
COMPUTATIONAL CHEMIST
(CADD*)
“I need to find hits for druggable
targets” (virtual screening)
DISCOVERY
HIT TO LEAD
MEDICINAL CHEMIST
PHARMACOLOGIST
“I need to optimize chemical structures
in order to improve affinity, selectivity
ADMET properties and decrease side
effects”
“I need to define relevant
pharmacological models on animals”
LEAD
OPTIMIZATION
COMPUTATIONAL CHEMIST
(CADD*)
COMPUTATIONAL CHEMIST
(CADD*)
“I need to optimize affinity and
selectivity of hits” (Structure based
design QSAR)
PRECLINICAL
“I need to optimize other
pharmaceutical properties while
maintaining affinity” (QSPR)
DEVELOPMENT
SYNTHETIC CHEMIST
“I need to define the easiest and most
productive way to reach my target
compound”
PROJECT MANAGER
“I need to be up to date with regards to
competitors working on the same subjects”
(Which compounds, targets are published in
Journals and/or patents)

10. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER
10
THE WORLD OF MEDICINAL CHEMISTRY AT YOUR FINGERTIPS
REAXYS MEDICINAL CHEMISTRY:
THE MOST POWERFUL AND VERSATILE MEDICINAL CHEMISTRY DISCOVERY ENGINE
ESSENTIAL INFORMATION
• 2.4 M chemical compounds
• 9 M biological experimental results
• 5100 Pharmacological targets
RELEVANT ANSWERS
• Chemistry driven searches
(Substructure/Similarity)
• Pharmacology driven searches
(Target, Cell, Bioassay)
• Taxonomies-driven searches
ACTIONABLE
• Intuitive and powerful
user-interface
• No access barrier
• Flexible export
(Manageable by user)

11. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER
REAXYS MEDICINAL CHEMISTRY : PATENTS COVERAGE
Patents Origin and starting date
US : 1971-present
EP : 1979-present
WO : 1978-present (English only)
Patents are coming from the A61K class
mainly but not only.
Patents count : 50632

12. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER
REAXYS MEDICINAL CHEMISTRY : JOURNALS COVERAGE
206421 articles are included in Reaxys Medicinal Chemistry
corresponding to 1047 Journals from 1980 to present.
Some articles stored in Reaxys Medicinal Chemistry are older than 1980.
1000 articles spread between 1979 and 1941.

13. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER
ESSENTIAL INFORMATION
COMPOUND
CHEMICAL STRUCTURE ,NAME, CODE, SYNONYM OF COMPOUND
DRUGGABLE TARGET
EXPLORE TARGET AFFINITY PATTERNS OF CHEMICAL COMPOUNDS
IN VITRO AND CELL BASED ASSAYS
IN VITRO ASSAYS (BINDING, SECOND MESSENGER ETC..) AND CELL BASED ASSAYS FOR EXAMPLE :
AGGREGATION, ANGIOGENESIS, APOPTOSIS, CELL DIFFERENTIATION, CELLULAR CYCLE, CHONDROGENESIS
ANIMAL MODELS DISEASE
OVARIECTOMIZED RAT IN OSTEOPOROSIS, TREATMENT OF GLAUCOMA, XENOGRAFTED ANIMALS WITH TUMORS TO TEST AND
DEVELOP ANTINEPLASTIC DRUGS
PHARMACOKINETIC AND ADME PROPERTIES
METABOLIC STABILITY, INTRINSIC CLEARANCE, HALF LIFE OF ELIMINATION, BIOAVAILABILITY, IN VIVO CLEARANCE
TOXICITY
CYTOTOXICITY, CARDIOTOXICITY, CHRONIC TOXICITY

14. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER
14
INTERACT WITH YOUR WORKFLOW
Link to full
text articles
Link to Reaxys:
‐ Compounds
‐ Citations
Link to full text
Patent: Espacenet
Link to Drug Bank
Link to Uniprot
Link to Embase
Link to Protein 3D
structure: PDB
Export data in
multiple formats:
Text, Excel, SDF, R
DF, XML files to be
incorporated
into third
party tools

15. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER
APPLICATION IN DRUG
DISCOVERY
15

16. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER
ACCESS TO KNOWLEDGE ALONG DRUG DISCOVERY CHAIN
Project
Kick off
- Indications for target
- Compound active on
target
- Most active
compounds
(IC50, Ki, EC50 < 50nM)
- Most active
competitors
- Target selectivity
- PK of Compounds
classes
- Adverse effects : CYPblockade
- Adverse effect :
hERG-activity
Compound
Library
- Focused Library
- hERG Model
- CYP Model
HTS/Virtual
Screening
- Calcium T Type
Channel
- Hit Generation :
customer story
- Phenotypic in silico
Screening
Hit to Lead
- High affinity towards
the target
- Show selectivity
versus targets
- Reduce binding to
HSA
- Improve cell
permeability
- Not be metabolized
rapidly
- Not interfere with
the P450 enzymes
-Not interfere with
the Pgp
- Show selectivity
versus targets
(Advanced)
- Multiple inhibitors :
Renin angiotensin
pathway
Lead
Optimization
- Exploration of
structural features
of a lead series of
Compounds
-Safety
pharmacology (off
Targets)
- Pharmacokinetics
- ADMET
- Computational
chemistry and
molecular modeling
16

17. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER
PROJECT KICK OFF
AKT1 INHIBITORS
17

18. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER
AKT INHIBITORS
•
AKT IS ASSOCIATED WITH TUMOR CELL SURVIVAL, PROLIFERATION, AND
INVASIVENESS.
•
THE ACTIVATION OF AKT IS ALSO ONE OF THE MOST FREQUENT ALTERATIONS
OBSERVED IN HUMAN CANCER AND TUMOR CELLS.
•
Akt1 has been implicated as a major factor in many types of cancer
•
Akt2 is an important signaling molecule in the Insulin signaling pathway
•
The role of Akt3 is less clear, though it appears to be predominantly expressed in the
brain
THEREFORE, UNDERSTANDING AKT AND ITS PATHWAYS IS IMPORTANT FOR THE
CREATION OF BETTER THERAPIES TO TREAT CANCER AND TUMOR CELLS.

19. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER
ABOUT AKT1 INHIBITORS IN REAXYS MEDICINAL CHEMISTRY
• MOST ACTIVE COMPOUNDS ON AKT1 (IC50, KI OR KD BELOW
0.05 µM?)
• TARGET SELECTIVITY (AKT1 VERSUS AKT2)
• PK OF COMPOUNDS CLASSES
• ADVERSE EFFECTS : CYP-BLOCKADE
• ADVERSE EFFECT : HERG-ACTIVITY

20. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER
PROJECT KICK OFF
LIVE DEMO
20

21. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER
IN SUMMARY
• Reaxys Medicinal Chemistry is a Powerful
solutions across the entire Drug Discovery
Workflow
• Designed to help Medicinal and Computational
Chemists in all sectors, advance more quickly
and confidently through their research.
21

22. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER
THANK YOU
QUESTIONS?
22

23. CLIQUEZ ICI POUR CHANGER LE TEXTE
THANK YOU
FOR MORE INFORMATION AND QUESTIONS PLEASE USE THE CONTACT DETAILS
ON OUR ONLINE PAGE.
OUR NEXT REAXYS WEBINAR IS ON OCTOBER 22. AND YOU MAY ALSO BE
INTERESTED IN JOINING OUR REAXYS WEBINARS. ALL WEBINARS MAY BE FOUND
ON OUR WEBINAR PAGE
ALL TRAINING AND SUPPORT MATERIALS ARE LOCATED AT
WWW.ELSEVIER.COM/ONLINE-TOOLS/REAXYS/CUSTOMER-SUPPORT
Please fill out the survey that
appears on your screen after
leaving the webinar.
23