1. Global Health Chemical Diversity Library

2. Abbreviations BMGF - Bill & Melinda Gates Foundation
Fsp3 - fraction of sp3 carbons
GHCDL - Global Health Chemical Diversity Library
HBA - hydrogen bond acceptor
HBD - hydrogen bond donor
Rot_Bonds - rotatable bonds
TPSA - topological polar surface area
UoD – University of Dundee

3. Introduction to the GHCDL
68,689 compound library
Designed for screening against the BMGF priority pathogens
Designed to interact with diverse range of biological targets
Commercially sourced compounds from reputable vendors
Library available for 25 screens over a 3 year period
Lead-like physicochemical properties with enhanced Fsp3 character
Filtered to remove unwanted groups
Enriched in novel chemotypes*
*Novelty defined as compounds dissimilar to compounds already known to have been screened against the
Bill & Melinda Gates Foundation priority pathogens

4. GHCDL physchem profile
Mean MW = 320.7
Mean logP = 2.0
Mean HBD = 0.9
Mean HBA = 5.6

5. GHCDL physchem profile
Mean TPSA = 64.2
Mean Rot_Bonds = 4.5
Mean Aromatic_Rings = 1.8
Mean Fsp3 = 0.48

6. Abbvie physchem tiering
GHCDL Tier
Mean Tier = 1.58
Bioorg. Med. Chem. 2012, 20, 4564–4573

7. Structural alerts
Library filtered using 3 sets of complementary structural alerts
Eli Lilly, PAINS and Dundee alerts
Remove chemically reactive/unstable compounds
Remove frequent hitters (fluorescent cmpds, redox active, aggregators etc.)
Remove known toxicophores
Eli Lilly: J. Med. Chem. 2012, 55, 9763−9772
PAINS: J. Med. Chem. 2010, 53, 2719–2740

8. High quality diverse chemotypes
>14,000 clusters
Average cluster size 5 compounds
Cluster size range compounds
Sourced from 19 vendors including:
Analyticon
Asclepia
Asinex
Bionet
Chembridge
ChemDiv
Chemroutes
ChemX
Edelris
Maybridge
Enamine
Interbioscreen
Life Chemicals
Princeton
Specs
Timtec
UORSY
Vitas
WuXi

9. What to expect Access to 68,689 compound library
Assay ready 384 well plates for the primary screen
Cherry picking for active confirmation at a single concentration
Dose response plate creation of confirmed actives
Data analysis using ActivityBaseTM protocols
Compound and data management provided by the Drug Discovery Unit (UoD)
Electronic file containing structures of library compounds with calculated properties and catalogue codes
Virtual libraries to aid hit expansion
4.5M compound drug-like library with properties and catalogue numbers
Smaller sets can also be accessed for lower throughput assays
8,890 compound set comprising 3 compounds per cluster (384 well)

10. How it works Screening centre BMGF & UoD UoD Abbreviation
Submit project proposal to UoD/BMGF
BMGF & UoD
Successful project assessment
Complete SOP template & send to UoD
UoD
Primary screen plates prepared & delivered to screening centre
Screening data generated & sent to UoD
Data analysed and sent to screening centre along with plate map
Hit selection/cherry pick list sent to UoD
Single concentration active confirmation plates sent to screening centre
Data generated & sent to UoD
IC50 pick list sent to UoD
Dose response plates sent to screening centre
Chembl
Data released to Chembl 1 year after final data release to UoD*
Abbreviation
UoD – University of Dundee
*All data received by the UoD will be made Public within 1 years of final data release to Univ. of Dundee. Release of data into the public domain can be delayed in cases were groups are still actively working on a chemical series derived from the library and require more time to secure an adequate intellectual property position. Data release may also be brought forward at the request of the originating screening centre.

11. FAQ’s Q. Who will assess my application to screen the GHCDL?
A. The University of Dundee guided by input from the Bill & Melinda Gates Foundation.
Q. Can I change my mind and screen the library against another target/pathogen?
A. The GHCDL should only be screened against the previously agreed target/pathogen in the previously agreed format.
Q. Why do we need to release our raw data?
A. The UoD and BMGF wish to capture high level data on the performance of the library e.g. hit rates, frequent hitter activity etc. The data and assay conditions will also be released into the public domain after 1 year to aid the research community working on diseases of the developing world.
Q. Does the data have to be released into the public domain after 1 year?
A. Data release can be delayed in cases were groups are still actively working on a chemical series derived from the GHCDL and require more time to secure an adequate intellectual property position.
Q. Can we patent compounds in the GHCDL?
At the discretion of the project, any derivatives of the GHCDL compounds and any intellectual property residing in those derivatives shall be owned by the party creating them. No party will seek to obtain any other intellectual property rights whatsoever in the GHCDL compounds including, without limitation, any new formulations, uses (medical or otherwise), applications or methods of administration thereof.

12. FAQ’s cont.
Q. Are there any restrictions around publications arising from the screening of the GHCDL? A. No. All publications should acknowledge the University of Dundee Drug Discovery Unit for the design and supply of the GHCDL. The University of Dundee may publish high level data on the performance of the library, no data will be published that would endanger the intellectual property position of any project. All parties will get appropriate acknowledgement in any data release or publication. Q. Who should I contact for further information? A. Professor Paul Wyatt, College of Life Sciences, University of Dundee, Dundee