ManagingInternalandExternalChemistryforEfficientDrugDelivery

DavidHollinshead(ElixirSo)ware)AndrewGriffin(PraxisPrecisionMedicines)

ChemistryWorkflow

BeforeGenomics(BG)–  Compounds(upto1gqty)–  Singlecompoundsynthesis–  Animalmodels–  Structure-effectrelaKonships

(ED50)–  Pharmacology–  ……

(DiseasetoTarget)

TheiteraKveHypothesis–Make–TestchemistryworkflowwasboundedbysmallcompoundnumbersandrelaKvelyfewmeasurements...

ChemistryWorkflow

Hypothesis

MakeTest

ChemistryDrivers

•  Improvequalityofcompounds;reduceaSriKon•  Delivermorecompounds;reducecycleKmeMoretools,technologies,datafordecision-making...– MoreandDesigntoolsanddesignapproachesfordevelopingleads

–  Chemicaltechnologiestoprosecutemanycompoundssimultaneously

–  Diversescreeningtestdatatoanalyze&interpret–  Improvingunderstandingofthereasonsdrugsfail

EssenKalChemistryWorkflow

PostGenomics(PG)–  Compounds(lowmgqty)–  ‘Combinatorial’HTchemistry–  HTassays–  Structure-acKvity

relaKonships(pKi)–  Molecularbiology–  ……

(TargettoDisease)

GenomicsdrivenchangesinHOWchemistryisdeployedandwhatguidesit.MOREdesignapproaches,compounds,measurements&dataanalysis...

ChemistryWorkflow

Design

Make

Test

Analyze

chemTraX|Goals

Design

Make

Test

Analyze

Capturedesignhypotheses&objecKves

Trackprogresswithdeliveryofagreedsynthesistargets

Triggeranalysis–wasthedesignobjec;vemet?Capturelearning...

Knowwhenbiologicalevalua;oniscompleted

Enhanceteam-working&communicaKonwithintheDMTAcycle

chemTraX|UserVisualizaKons

ProjectDashboard

DesignTracking

CompoundTracking

ProjectDashboard

•  FlexiblefuncKonalitytoviewprojectdesignsetsinmanyways•  WeviewtheinformaKonwithworkflowasthe‘process’androwedby‘priority’•  Extradimensiontothedatausingcoloring,intheexamplebelowcolorbychemicalseries•  FilteringofinformaKontoenablefocussedviews

Highleveldatashown:Title,series,numberofCompounds,chemistHoverovershowsmoreinfo

WhatInformaKonDoWeCaptureWithinADesignSet?

•  Notjustalistofcompounds•  InformaKoncapturedcanbetailoredtoeachorganizaKon’sneeds•  Capturingofhypothesis,issuetosolveandoutcomeofdesignsetcanalsobecaptured

•  Knowledgecaptureandsharing•  SensiKveinformaKonlike‘hypothesis’canbehiddenfromexternalpartners

RealKmeTeamCommunicaKon(InternalandExternalMembers)

‘Comments’toshareupdateswithexternalpartnersandforexternalpartnerstoshareinformaKonbacktotheclient‘ASachments’toshareexternally(e.g.syntheKcprocedures)orinternallyonly(e.g.compchemdockingposes)

TargetsWithinTheChemistryTab

Workflowviewofcompoundsinadesignset

•  Prioritycanbegivetoindividualcompounds•  Compounddraganddroptoupdatestatus•  Compoundscanbeassignedtoindividualchemistsifrequired(manageworkload)

SpreadsheetViewofCompounds

Compoundstatus(forsynthesis,insynthesisetc)

CalculatedproperKes(generatedwhencompoundsloadedintoChemTraX)

•  EasyviewofbasiccalculatedproperKesforeachcompound•  QuickedittoprioriKze/downprioriKzecompounds•  PopularwithPraxisusers