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Minin r mi
substructuresin
PubChem using
mo ecu armatc ingpairs
OlegUrsu
Universit of New Mexico
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Hitsinman unrelatedHTSassa s
Promiscuouscompounds
(aggregation,
reactive,
etc.)
Assayinterference(fluorescence,quenchers,etc.)
xperts now e ge ru es
Not
available
in
public
domain
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Molecularmatchingpairs
CH3
Cl
Molecularpair Moleculartransformation
N
CH3
N
CH3
H
OHO
H
OHO
Mefenamic acid Tolfenamic acidSingle
cut
S
HNO
O
NH
NH
S
NHO
O
*"
*
*"
*
Sulfaguanole Sulfamoxole
Doublecut
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MMPsapplicationsand
Identifymoleculartransformationsinaseries
Mapmoleculartransformationstochangesin
Study
bioisosterism,
activity
cliffs,
SAR u eopt m zat ono :aqueousso u ty,
plasmaproteinandhERG biding,P450
Leatherface1,WizePairZ2,Hussain3
1. Cheminformatics inDrugDiscovery,2004,271285
2. J.Chem.Inf.Model.2010,50,13501357
3. J.Chem.
Inf.
Model.
2010,
50,
339
348
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PubChem database
Chemicalandbiologicalactivitydatabase,NIH
funded
Datadeposited
by
9Molecular
Libraries
centers
Total Molecular LibrariesSu stances ~85mi ~ 400
Assays 504,228 3,860(0.77%)
Screeningdatapoints ~142mil ~134mil(94%)August2011
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Promiscuousfragments
H3C
S
N
X Testedassays Activeassays
O
Cl
Cl
26731534
354 1
*
24792062
354 1NH
O
OO
es e
assaysActiveassays75
26728462
26728988
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O
Cl H
O
O
OH Cl H
O
OH
OH OHC
H2
O CH3
3
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Promiscuit
score
.)(.
.
mm sactive
substtestedmediansubsttested
substactivescore
#ofsubstanceswith1ormore
activeMMPs
)(
assaysactive
mmpstestedmedianmmpstested
#distinct
assays
with
1or
fragment
1600)(
samplestestedmediansamplestested
samplesactive#ofsamplesmappedtoeach
activeMMPinanassa
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Toppromiscuousfragments
testedsubstances/activesubstancestested
MMPS/active
MMPStestedassays/activeassays
testedsamples/activesamplespromiscuityscore
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Promiscuityscoredistribution
singlecut
MMPs
777 931uni ue
doublecutMMPs
73,191unique
triplecutMMPs
53,993numberof
uniquefragments
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CH3
Cl
SN
A1
O
A
1
SS
O
HN
O
N+
O
A1
O
A1
OO
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patternsin
adatabase
of
biological
activities
I/O;
fragmentation;
SMARTS
match/generation;
depiction
Questions?
