reaxys medicinal chemistry oct2014

REAXYS MEDICINAL CHEMISTRY

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Quickly Assess Substance-Target Interactions with the Heatmap

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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 substances25 million biological datapointsfrom over 5,000 journalsand over 90,000 Patents

COMBINED USER INTERFACE

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Tramadol

IN VITRO

EFFICACYIN VIVO

ANIMAL

MODEL

TOXICITY/

SAFETY

PHARMACOLOGY

METABOLISM

PHARMACOKINE

TIC

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Data needs to be:

• Organized• Normalized• Compared

HOW CAN ALL THIS DATA BE USED EFFECTIVELY?

pX values are calculated from the data so you can:

• better compare biological results across publications (articles and Patents) and bioassays.

• Use third party tools (Spotfire, Pipeline Pilot) through the export.

SOLUTION: USE PX VALUES

HEATMAP

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HOW DO YOU COMPARE PX VALUES?

Filters to narrow down Manage X and Y

axis

Bioactivity data based on pX values

HOW IS REAXYS MEDICINAL CHEMISTRY RELEVANT?

NEW DRUG DISCOVERY PROJECT TASKS

- SAR ON KNOWN INHIBITORS OF PROPOSED TARGET- SCAFFOLD SEARCHING- TARGET SELECTIVITY- DEFINING IP SPACE OF SCREENING HITS [NOT DEFINED]- SYNTHETIC FEASIBILITY OF SCREENING HITS [NOT DEFINED]- VIRTUAL SCREENING

CURRENT DRUG DISCOVERY PROJECT TASKS

- METABOLIC STABILITY DATA- CYTOCHROME P450 INHIBITION- PK DATA- ANIMAL MODELS - DRUG DOSING- TOXICITY DATA- EXPLORATION OF STRUCTURAL FEATURES OF A LEAD SERIES OF COMPOUNDS

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DEMO

FIND IN VITRO ACTIVITY DATA FOR A SCAFFOLD

MINE RMC FOR CYTOCHROME P450 INHIBITION

PK DATA SEARCH

TOX DATA SEARCH

TARGET SELECTIVITY

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FIND IN VITRO ACTIVITY DATA FOR A SCAFFOLD

FIND IN VITRO ACTIVITY DATA FOR A SCAFFOLD

Select Bioassays

MINE RMC FOR CYTOCHROME P450 INHIBITION

MINE RMC FOR CYTOCHROME P450 INHIBITION

Select Effects

MINE RMC FOR CYTOCHROME P450 INHIBITION

Click rows to select them. Then click Limit to.

Sort to get the most active at the top of the list.

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Select the Substances tab. Then click the Output button

MINE RMC FOR CYTOCHROME P450 INHIBITION

PK DATA SEARCH

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Select the Substances tab.

PK DATA SEARCH

Then view the data and select data to add to a report. Click the Report button to open the report.

TOXICOLOGICAL DATA

TOXICOLOGICAL DATA

Filter by Target Species.

View by Target Species and by Parameters.

Sort by Activity in descending order.

Select the Substances tab.

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Click the Lookup link and then select the 2 target names.

WHICH SUBSTANCES ARE ACTIVE AGAINST TRPA1 BUT NOT TRPV1?

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These are the columns for TRPA1 and TRPV1

These columns appear because some of the substances were tested against these targets in the same assays for TRPA1 and TRPV1.

Select the columns, click the grey box, and select Delete Selected Columns.

WHICH SUBSTANCES ARE ACTIVE AGAINST TRPA1 BUT NOT TRPV1?

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WHICH SUBSTANCES ARE ACTIVE AGAINST TRPA1 BUT NOT TRPV1?

Substances with low affinity to TRPV1and high affinity to TRPA1

Substances with similar activity values

Substances with low affinity to TRPA1 and high affinity to TRPV1

Sort one of the columns in Descending order. Then sort the other column and scroll and compare.

THANK YOU!

ANY QUESTIONS?

CONTACT ME: C.FLEMMING@ELSEVIER.COM

PLEASE FILL OUT THE SURVEY AT THE END OF THE WEBINAR

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