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Using ChemAxon Toolkits in theUsing ChemAxon Toolkits in theLead Discovery Database at GNFLead Discovery Database at GNF

Genomics Institute of the

Novartis Research

Foundation

Genomics Institute of the

Novartis Research

Foundation

Hayk Asatryan, Dimitri etrov,

!" Frank #an, Andrey!antrosyan, $aisheng Chen,!h%mei &iang, &e' &anes,

#ingyao (ho%

)ay, *++)ay, *++-%da.est, H%ngry-%da.est, H%ngry

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!co.e o/ the Lead Discovery Database!co.e o/ the Lead Discovery Database0 LDD-0 LDD-

Compound

Management

Center

HTS

Center

Program

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Genomics Institute of the

Novartis Research

Foundation

Genomics Institute of the

Novartis Research

Foundation

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7/25/2019 B1 ChemAxonMeeting Print 1

3/16

$ata Mining

)racle +

$aCart

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Marvin #pplet

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Compound RegistrationNormali*ation 1Novartis2

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Architect%re o/ LDD-Architect%re o/ LDD-

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Genomics Institute of the

Novartis Research

Foundation

Genomics Institute of the

Novartis Research

Foundation

bl / h

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roblems o/ the Heterogeneo%sroblems o/ the Heterogeneo%s!et%.!et%.

)olsmart sol%tion /or1H2N31H24c5ccccc56nstead o/

1H2N31H24c5ccccc51N78H+78H52c5ccccc5

)ol*!mi 9 aromati:ation ;)ol*!mi 9 aromati:ation ;chiralitychirality

Nitrogen Nitrogen

C?C3@N=4c5ccccc5"C?C3@N?4c5ccccc5C?C3@N=4c5ccccc5"C?C3@N?4c5ccccc5

ChemDraB ; )arvinChemDraB ; )arvin

)ol!mart 9 chirality)ol!mart 9 chirality

NH

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, draB6n.%t> C?C@C=C%t.%t>1E2C@C1E2

Genomics Institute of the

Novartis Research

Foundation

http://sumatra.gnf.org/Intranet/MainPageServlet

7/25/2019 B1 ChemAxonMeeting Print 1

5/16

Daylight ; ChemAxon 3disc%ssDaylight ; ChemAxon 3disc%sslater4later4Accord> chirality, dis.layAccord> chirality, dis.lay

ricing considerationsricing considerations

roblems o/ the Heterogeneo%sroblems o/ the Heterogeneo%s

!et%. 3cont"4!et%. 3cont"4

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Accord /or

7/25/2019 B1 ChemAxonMeeting Print 1

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&Chem Cartridge 9 initial testing&Chem Cartridge 9 initial testing3&%ly *++43&%ly *++4

Daylights s%bstr%ct%re search> 0E seconds&Cart s%bstr%ct%re search> 5+05* sec 3caching the Bholestr%ct%re table in racle4!imilarity search is a..roximately +0+ min%tes

35"Emillion4&Chem res%lts> 5+"E min%tes /or I million str%ct%res 3I GH:enti%m 4

!miles!miles Co%ntCo%nt Time 3ms4Time 3ms4

NC3@4C3@NC4c5csc3N4n5NC3@4C3@NC4c5csc3N4n5 ** 5*+5*+

C3@4c5cc34c34c34c5C3@4c5cc34c34c34c5 I+I+ 5*+J55*+J5

C5CC3C43N4C34C3C45C5CC3C43N4C34C3C45 II 55*+55*+c5ccc3!3@43@44cc5c5ccc3!3@43@44cc5 KK 5+KI5+KI

C*C3n5ccc3@41nH2c5@4C34C*C*C3n5ccc3@41nH2c5@4C34C* ++ 5+I5+5+I5+

Cc5ccc3N3CCCl4CCCl4cc5Cc5ccc3N3CCCl4CCCl4cc5 IEIE 55K*55K*

C5C3C4C34C3C4C5CC5C3C4C34C3C4C5C *KI*KI 5*5E5*5E

C5C3C4C34C3C3N4@4C5C5C3C4C34C3C3N4@4C5 ** 5+K5+K

NC3@4C3N4Cc5cnc1nH25NC3@4C3N4Cc5cnc1nH25 I5I5 5K+555K+55

C3@4c5cc3C4c3C4c3C4c5C3@4c5cc3C4c3C4c3C4c5 IEIE 55J55J

C5C3C4C34C3C3N4@4C5C5C3C4C34C3C3N4@4C5 ** 5+E5+E

c5c3C41nH2c3@41nH2c5@c5c3C41nH2c3@41nH2c5@ ++ 5+J5J5+J5J

C3@4NC3C@4CCCNC3@N4NC3@4NC3C@4CCCNC3@N4N 5KI5KI 55K55KGenomics Institute of theNovartis ResearchFoundation

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-rainstorming-rainstorming6nitial attem.ts

ed%ce !As overhead

T%ning on nger.rint .arameters Bhen creating thestr%ct%re table

bservation!

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er/ormance Testing 9er/ormance Testing 9

!%bstr%ct%re !earch!%bstr%ct%re !earch

&Chem Cartridge 3sec4

DayCart3sec4

&Cart 3sec4

DayCart 3sec4

Genomics Institute of the

Novartis Research

Foundation

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N C id F !QLN C t id F t !QL

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NeB Cartridge Feat%res 9 !QLNeB Cartridge Feat%res 9 !QL

FilteringFiltering

Genomics Institute of the

Novartis Research

Foundation

Use ltering can dramatically im.rove.er/ormance

!QL Cost> *+secselect co%nt3R4 /rom c.d Bhere

ScMcom.are3ScMsmiles,c5ccccc5,se.@8 t>s4@5

!QL Cost> +"*sec

select R /rom c.d BhereScMcom.are3ScMsmiles,c5ccccc5,se.@8 t>s8lterQ%ery>select c"roBid /rom c.dMinstance i, c.d c Bherei".lateMsid@*EK5J5 and i"c.dMsid@c"c.dMsid4@5

Challenge> Bhen !QL0ltering is a..ro.riate!QL Cost> *secselect R /rom c.d Bhere

ScMcom.are3ScMsmiles,CCCCCCc5cccc3C@NCC34Cc*cccc3c*4C3C4C4c5,se.@8 t>s8lterQ%ery>select c"roBid /romc.d c Bhere c.dMsid+4@5

!QL Cost> +"*secselect co%nt R /rom c d Bhere

D C t t &C t )i tiD C t t &C t )i ti

7/25/2019 B1 ChemAxonMeeting Print 1

11/16

DayCart to &Cart )igrationDayCart to &Cart )igrationChallengesChallenges

6dentical str%ct%res or not6dentical str%ct%res or not

TBo identical str%ct%res considered byTBo identical str%ct%res considered by

Daylight ideally remains identical by &Chem,Daylight ideally remains identical by &Chem,and vice versa"and vice versa"

Aromatic !%l/%r Aromatic !%l/%r

CC5@NC3@N!3@N54C*CCCCC*4ClCc5nc3Cl4ns3n54C*CCCCC*

Genomics Institute of the

Novartis Research

Foundation

!ol%tion> &chem s%..ortDaylight r%les

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Challenges 9 6dentical !tr%ct%resChallenges 9 6dentical !tr%ct%res

3cont"43cont"4-rc5ccc*1N2cInccccccncI0c*c5-rc5ccc*NcInccccccncI0c*c5

Non0standard -ond Non0standard -ond

Chirality ChiralityC1CV2534C1CVV2*IC1CVH234CC3CCC@CC3@4CC1CV2C4CICCC5*

Rc5ccc3CCC*CCC@C*4cc5Rc5ccc3CCC*CCC@C*4cc5

or NULL 3not s%..orted byor NULL 3not s%..orted by&Cart4&Cart4

6ncom.lete !tr%ct%res in Database6ncom.lete !tr%ct%res in Database

Genomics Institute of the

Novartis Research

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)igration Challenges 0 Log)igration Challenges 0 Log+O com.o%nds have both val%es agreed Bithin I

Genomics Institute of the

Novartis Research

Foundation

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A..lications in LDD-A..lications in LDD-!tr%ct%re Dis.lay6nstead o/ %sing )arvin a..lets /orstr%ct%re dis.lay, LDD- %ses

a str%ct%re image servlet" This strategyim.roves dis.lay s.eed, overcomes%ndesirable broBser caching"

!tr%ct%re !earch

6n0ho%se and vendor collection,/olloBedby hit analysis"

Click on animage /or

)arvina..let

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Genomics Institute of the

Novartis Research

Foundation

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ngoing Develo.ments ngoing Develo.ments

ther a..lications

0gro%. analysis)ost0common s%bstr%ct%re analysisDatabase0Bise cl%stering analysis

Thank #o%8

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Genomics Institute of the

Novartis Research

F d ti