Royal Society of Chemistry developments to support open drug discovery

Antony Williams, Ken Karapetyan, Valery Tkachenko, Colin Batchelor Alexey Pshenichnov and Jon Steele

ACS Dallas

March 2014

Supporting Open Drug Discovery

• As a publisher

• As a host of chemistry databases

• As a charity and community support

• As a provider of grant-based services

• As an innovator in cheminformatics

RSC as a Publisher• One of the world’s top publishers for chemistry

– journals, books and databases

• High quality, high impact journals – direct journals of relevance for drug discovery

• Databases to support drug discovery – Merck Index, ChemSpider, Natural Product Updates…

• Innovative publisher – semantic markup, mobile developments

• ~30 million chemicals and growing

• Data sourced from >500 different sources

• Crowdsourced curation and annotation

• Ongoing deposition of data from our journals and our collaborators

• Structure centric hub for web-searching

As host of chemistry databases

ChemSpider

ChemSpider

Properties – ACD/Labs

Properties – EPI Suite

Properties - ChemAxon

Literature references

Patents references

Books

Chemical vendors and data sources

ChemSpider

• Ongoing expansion of integrated services of value to open drug discovery• Integration to Mcule online docking and

toxicity checker – in development• New grant to integrate to improved patent

service with Cambridge IP (UK)• Integration to enhance MedChemComm

journal articles for property extraction and data management

ChemSpider SyntheticPages

ChemSpider SyntheticPages

ChemSpider Reactions

ChemSpider Spectra

RSC as a Charity

• Acts as host and funder for networking meetings

• Funds trainings and onsite participation

• Provides funding for RSC cheminformatics team to work on open drug discovery projects

Open Source Drug DiscoveryIndia

• Tuberculosis kills 1.6-1.7 million people every year (~1 every 8 seconds)

• 1/3 of the worlds population is infected

OSDD Collaboration

Recently sponsored cheminformatics jamboree – training by skilled specialists in the applications of cheminformatics to medicinal chemistry and drug design

OSDD Collaboration

• We will provide access and support to the ChemSpider API to integrate to their OSDD cheminformatics platform

• We will extend our data model to support their Open Data – compounds, pharmacology data

• Synthetic reactions will be published to ChemSpider SyntheticPages and Reactions

• Analytical Data to be published to ChemSpider Spectra

As a provider of grant-based services

• RSC cheminformatics participates in multiple European consortium-based grants• PharmaSea (FP7 funded)• Open PHACTS (IMI funded)

• RSC hosts the UK National Chemical Database Service (http://cds.rsc.org)

Antibiotic resistance

Discovery Curve Decay

Focus on Marine Natural Products

• RSC cheminformatics support to include:• Provide access to natural products subset

(make available on ChemSpider)• Develop “dereplication techniques”

• Searching NMR features against database• Develop advanced searches for MS data

• Host Open Data from the PharmaSea project and make available to the community

Marinlit

• RSC acquired Marinlit. Goes online in April

• All Marinlit chemical compounds in ChemSpider

• Marinlit developers are dereplication experts

Cancer Deaths Worldwide

Top Treatments for Cancer

• Over half of all drugs introduced between 1940 and 2006 were of natural origin or inspired by natural compounds

Importance of Natural Products

Natural Products for all of us!

Natural Products Data Availability

• 3-year Innovative Medicines Initiative project

• Integrating chemistry and biology data using semantic web technologies

• Open source code, open data and open standards

• Academics, Pharmas, Publishers…• To put medicines in the pipeline…

The Open PHACTS community ecosystem

Chemistry RegistrationNormalisation & Q/C

• New Chemical Registration System• Utilizes ChemSpider Validation

and Standardization platform• Utilizes FDA rule set as basis for

standardizations • Generate Open PHACTS identifier

(OPS ID)

O H

O

O H

O

O–

O

Na+

Na+

O

O–

O

O–

OPS1

O–

ONa

+

DrugBank ID DB07241

OPS5OPS4

OPS3

OPS2

OPS6

ops:OPS1 skos:exactMatch <http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB07241> .

ops:OPS2 skos:relatedMatch ops:OPS1 .

ops:OPS3 skos:relatedMatch ops:OPS1 .

ops:OPS3 skos:closeMatch ops:OPS4 .

ops:OPS3 skos:closeMatch ops:OPS5 .

ops:OPS4 skos:closeMatch ops:OPS6 .

ops:OPS5 skos:closeMatch ops:OPS6 .

ChemSpider Validation & Standardization Platform

Quality Assurance

Open Sourcing Data and Code

• All Open PHACTS data is licensed as Open Data and available from Open PHACTS website – ca. 2 Million chemicals

• The Chemical Registration Service, including Chemical Validation and Standardization Platform will be released as Open Source code to the community (from Open PHACTS github site)

Enabling Academic ResearchersUK National Chemical Database

Data for the Community

• Data on ChemSpider is curated in an ongoing fashion - take what you need!

• Used a lot for accessing the “dictionary of chemicals” to build models – right Sean?

• Pharmacalogy data will increasingly be available – from PharmaSea and OSDD

• All Open PHACTS data already available!

As Innovator in Cheminformatics

• Hopefully self-evident by now?• ChemSpider• Support of Open PHACTS, PharmaSea and

Chemical Database Service• Releasing Open Source code to community

• To come:• Chemical Data Repository in development• Hosting models for the community

We are doing it…we will do more

Royal Society of Chemistry developments to support

open drug discovery

Thank you

Email: williamsa@rsc.orgORCID: 0000-0002-2668-4821 Twitter: @ChemConnectorPersonal Blog: www.chemconnector.com SLIDES: www.slideshare.net/AntonyWilliams