Community-based approach to research on infectious
diseases of the developing world and global health
Rita Stanikunaite PhD, Arnas Palaima PhD, Barry A. Bunin PhD
Collaborative Drug Discovery
Collaborative Drug Discovery (CDD, Inc.), 1818 Gilbreth Road, Suite 220, Burlingame, CA 94010
ABSTRACT
Currently, infectious diseases of the developing world (e.g., malaria, tuberculosis)
represent a global health challenge of the 21st century and require new approaches that
would allow scientists to do research more effectively. As a result of the development of
web-database technologies, recently a community-based approach to research on
infectious diseases of the developing world and global health has emerged. The major
components of effective scientific community include: (1) unifying goal, or focus on
common therapeutic areas/diseases; (2) multiple research areas/expertise; (3) uniform
database platform that allows effective data accumulation and management; (4) easy
access and sharing of information; (5) potential for unlimited growth. The Collaborative
Drug Discovery (CDD) database built by utilizing community-based web technologies
currently provides a platform that allows scientists to archive, mine, and share research
data with a focus on infectious diseases of the developing world. This new collaborative
technology allows researchers to build up networks of technical experts around
therapeutic or target areas thus facilitating discovery of new drug candidates. It allows
scientists to speed up the research by sharing unpublished data providing new hope in
the race to overcome drug resistance. An example illustrating how potential
chemosensitizers to address chloroquine resistance could be identified by using the CDD
database platform is presented.
Typical
TypicalLab:
Lab:The
TheData
DataExplosion
ExplosionProblem
Problem
Scientific
Scientific Community
Community
What
What isis needed
needed to
to build
build an
an effective
effective scientific
scientific
community?
community?
••unifying
unifyinggoal,
goal,or
orfocus
focuson
oncommon
commontherapeutic
therapeuticareas/diseases
areas/diseases
••multiple
multipleresearch
researchareas/expertise
areas/expertise
••uniform
uniformdatabase
databaseplatform
platformfor
fordata
dataaccumulation
accumulationand
andmanagement
management
••easy
easyto
toaccess
accessand
andshare
shareinformation
information
••potential
potentialfor
forunlimited
unlimitedgrowth
growth
Infectious
InfectiousDiseases
Diseasesof
ofthe
theDeveloping
DevelopingWorld
World
Malaria,
Malaria,tuberculosis,
tuberculosis,Chagas
Chagasdisease,
disease,Leishmaniasis,
Leishmaniasis,African
African
sleeping
sleepingsickness,
sickness,etc.
etc.
••global
globalhuman
humanpopulation
populationisisaffected
affected
(e.g., malaria alone kills 1-3 million people and causes disease in 300-500 million people
annually)
(e.g., malaria alone kills 1-3 million people and causes disease in 300-500 million people annually)
••fast
fastgeneration
generationofofdata
data
••data
dataisisininaaform
formwhich
whichmakes
makesitithard
hardtotoprocess
process
••data
dataoften
oftenfragmented
fragmentedand
anddisorganized
disorganizediningroups
groups
••urgent
urgentneed
needfor
foreffective
effectivedrugs
drugs
st
Global
GlobalHealth
HealthChallenge
Challengeof
ofthe
the21
21stCentury:
Century:
Drug
DrugResistance
Resistance
••scientists
scientistsneed
needtotofind
findways
waystotodevelop
developdrugs
drugsfaster
fasterthan
than
pathogens
pathogensdevelop
developresistance
resistance(e.g.,
(e.g.,malaria,
malaria,tuberculosis)
tuberculosis)
••aalot
lotofofvaluable
valuabledata
dataremains
remainsunpublished
unpublishedand
andisisnot
not
accessible
accessibletotocolleagues
colleagues
••web-based
web-basedsimultaneous
simultaneoussharing
sharingresearch
researchdata
datacould
couldspeed
speed
up
upthe
thedrug
drugdiscovery
discoveryprocess
processand
andaddress
addressdrug
drugresistance
resistance
The
TheCollaborative
CollaborativeDrug
DrugDiscovery
Discovery(CDD)
(CDD)database
databasebuilt
builtby
byutilizing
utilizingcommunity-based
community-basedweb
webtechnologies
technologiescurrently
currentlyprovides
providesaaplatform
platformthat
thatallows
allowsscientists
scientiststoto
archive,
archive,mine,
mine,and
andshare
shareunpublished/published
unpublished/publisheddata
datawith
withaafocus
focuson
oninfectious
infectiousdiseases
diseasesof
ofthe
thedeveloping
developingworld
world
• provides an easy to use, searchable database format to effectively archive and mine research data
• allows the creation of virtual drug discovery networks within scientific community to speed up research
• web sharing of unpublished data could save time/resources and prevent duplication of results
• data can be selectively shared with other scientists or openly shared within the whole scientific community
CDD Scientific Communities
Current
CurrentTherapeutic
TherapeuticTargets
Targets
e.g.,
e.g.,malaria,
malaria,tuberculosis,
tuberculosis,Chagas
Chagasdisease,
disease,Leishmaniasis,
Leishmaniasis,African
Africansleeping
sleepingsickness
sickness
Global
GlobalResearch
Research
USA,
USA,Europe,
Europe,South
SouthAfrica,
Africa,Australia
Australia
University
UniversityofofCaliforniaCalifornia-San
SanFrancisco,
Francisco,Stanford
StanfordUniversity,
University,University
UniversityofofWashington,
Washington,
University
of
Pennsylvania,
University
University of Pennsylvania, UniversityofofCaliforniaCalifornia-Berkeley,
Berkeley,University
UniversityofofCaliforniaCalifornia-Los
Los
Angeles,
Angeles,Burnham
BurnhamInstitute,
Institute,St.
St.Jude
JudeChildren’s
Children’sResearch
ResearchHospital,
Hospital,University
UniversityofofCape
CapeTown,
Town,etc.
etc.
Case example of community collaborative drug discovery applied to malaria
Drug Resistance in Malaria:
The Case of Chloroquine
Some Chemical Approaches to Drug
Resistance Reversal
Use of chemosensitizers or resistance reversal
agents
OMe
N
OMe
N
OMe
New Strategies to Overcome
Chloroquine Resistance
Use CDD community database for potential
chemosensitizers
- mining compounds with chemosensitizer
pharmacophore
- e.g., Dr. McKerrow group237 compounds with Ar(C)4NC
pharmacophore
verapamil
OMe
Multiple
MultipleResearch
ResearchAreas/Expertise
Areas/Expertise
e.g.,
e.g.,biology,
biology,chemistry,
chemistry,pharmacology
pharmacology
- -search
for
new
molecular
search for new moleculartargets
targets
- -search
searchfor
foractive
activecompounds
compounds
- -bioassay
bioassaydevelopment
developmentand
andscreening
screeningofofcompounds
compounds
- -understanding
understandingdrug
drugresistance
resistancemechanisms
mechanisms
- -other
other
Open
OpenAccess
AccessData
Data
- -chemoinformatics
chemoinformaticsdata
dataononFDA
FDAand
andOrphan
Orphanapproved
approveddrugs
drugs(Dr.
(Dr.Lipinski)
Lipinski)
- -modern
modernmalaria
malarialiterature
literaturedata
datalinked
linkedtotogenes
genes(Dr.
(Dr.Roos,
Roos,U.U.ofofPennsylvania)
Pennsylvania)
- -modern
malaria
literature
data
linked
to
assays
(Dr.
Gelb,
U.
of
Washington)
modern malaria literature data linked to assays (Dr. Gelb, U. of Washington)
- -army
armymalaria
malariascreening
screeningdata
data(>(>15,000)
15,000)dating
datingback
backtotoWW-II
WW-II(Dr.
(Dr.Guy,
Guy,St.
St.Jude
JudeCRH)
CRH)
- -“Open-Content”
“Open-Content”drug
drugdiscoverydiscovery-Trypanosoma
Trypanosomabrucei,
brucei,T.T.cruzi,
cruzi,Schistosoma
Schistosomamansoni,
mansoni,
Leishmania,
Leishmania,Plasmodium
Plasmodiumfalciparum
falciparum(Dr.
(Dr.McKerrow,
McKerrow,U.U.ofofCaliforniaCalifornia-San
SanFrancisco)
Francisco)
Collaborative Network
SAR in chemosensitizers
www.rsc.org/…/News/2006/June/03070601.asp
A proposed (revised) basic chemosensitizing
pharmacophore hypothesis in malaria
S
(C)n
R
S'
S = C, N, O;
R = Alkyl, Aromatic
S’ = N, Aromatic
n≥2
e.g., Ar-(C)4-N-C
www.texasaps.org/global/
Dr. Kelly Chibale, U. of Cape Town
Acknowledgments:
Dr. Kelly Chiballe, University of Cape Town
Dr. James McKerrow, University of California, San Francisco