reaxys medicinal chemistry nov20 2014
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REAXYS MEDICINAL CHEMISTRY
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Drug Repositioning (Repurposing)
Christine Flemming
c.flemming@elsevier.com
Webinar held November 20, 2014
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DRUG REPURPOSING
ScopusReaxys
Literature search shows increasing interest in drug repurposing
“BIG PHARMA” DRUG DISCOVERY IN THE 21ST CENTURY
The Problem: The pharmaceutical industry is short of new drugs.
In the 2nd part of the 20th century, about 50-60 new drugs (NCEs) were approved by
the FDA every year.
In contrast, in 2002, a historical low of 17 NCEs were approved (in 2001, 24 NCEs, in
2000, 27 NCEs, in 2003, 21 NCEs).
RESEARCH COST
research costs for a
new drug are
estimated to be in
the $1-1.5 Bi. range.
Considering all high-
profile failures in
recent drug discovery,
this figure is unlikely
to drop substantially
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DRUG REPURPOSING
• Fewer safety concerns
• Saves money
• Less time to get a drug to market
• New opportunities
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Reaxys Reaxys Medicinal Chemistry
TWO DATABASES
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Reaxys
TWO DATABASES
Searches over 50 million unique substances
Physical properties
Spectra data
Reaction information
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Reaxys Medicinal Chemistry
TWO DATABASES
Contains over 5 million substances
25 million biological datapoints
from over 5,000 journals
and over 90,000 Patents
COMBINED USER INTERFACE
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ESSENTIAL INFORMATION: 100+ EXPERIMENTAL FIELDS
Reaxys Medicinal Chemistry excerpts all the relevant Quantitative data
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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
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Reaxys Medicinal Chemistry can be used for:
• The assessment of new drugs
• Lead identification
• Lead optimization
• Drug repurposing
DRUG PROFILE
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KETAMINE
Used as an anesthetic for the past 50 years
Over the last 5 years there has been increased interest in studying it’s use in mood disorders, as a vasodilator, and as an antinflammatory, among other things.
Use Reaxys Medicinal Chemistry to get a profile of Ketamine and related drugs
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DRUG PROFILE
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KETAMINE
EXAMPLE OF THE RAW DATA
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EXPORT THE DATA
DRUG PROFILE
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KETAMINE
Used as an anesthetic for the past 50 years
Over the last 5 years there has been increased interest in studying it’s use in mood disorders, as a vasodilator, and as an antinflammatory, among other things.
Use Reaxys Medicinal Chemistry to get a profile of Ketamine and related drugs
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FIND SUBSTANCES SIMILAR TO KETAMINE
CAN THESE SUBSTANCES SUGGEST OTHER POSSIBLE USES FOR KETAMINE?
FOCUS ON SUBSTANCES WITH DIFFERENT TARGET DATA
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Compare to Ketamine targets
Show structures
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FIND OUT MORE ABOUT THE KETAMINE NMDA TARGET
Use these 2 fields for the query
Sort the Agonist column in descending order to view the most active substances.
View Effects/Substances
WHAT OTHER SUBSTANCES BIND TO THIS TARGET? CAN I SEE JUST THE AGONISTS?
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View the data for these substances. For example:
Note: This one should be the last one in the list.
SEARCH BY EFFECT
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MARKETED DRUGS
Look for drugs that have antiparasitic/antiprotozoal activity and are currently on the market. Which targets are involved in their activity?
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Antihypertensive
vasodilator Cough suppressant
antioxident
Some substances in the list are marketed for other things, such as:
WHICH TARGETS ARE RESPONSIBLE FOR THE ANTIPARASITIC/ANTIPROTOZOAL ACTIVITY?
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Change the Heatmap view
View the data
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WHICH SUBSTANCES HAD THE HIGHEST PX VALUES?
WHAT BIOLOGICAL SPECIES WERE THEY TESTED ON?
Change the Heatmap view
Filter for pX >5.9
Limit the view to selected products that may warrant further investigation
Used in eye drops for eye infections.
Used for cutaneous T-cell lymphoma
A Natural Product for use in for a variety of illnesses
SELECT DATA TO ADD TO A REPORT
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Switch to Substances view
View Data Availability
Mouse over the data and select the data you want to add to a report.
View and manage the Report by clicking the Report button.
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