grant
Lead Optimization and Preclinical Development of a small molecule inhibitor of M. avium KasA
Organization HACKENSACK UNIVERSITY MEDICAL CENTERLocation HACKENSACK, UNITED STATESPosted 20 Jun 2025Deadline 31 May 2030
NIHUS FederalResearch GrantFY2025Abnormal Assessment of MetabolismAccelerationAminesAnabolismAnimal ModelAnimal Models and Related StudiesAnimalsAnsamycinAssayBacterial InfectionsBattey BacillusBindingBinding SitesBioassayBioavailabilityBiochemicalBiochemistryBiological AssayBiological AvailabilityBiological ChemistryButaneCell BodyCell WallCellsChronicCombining SiteComplexCrystallizationDataDeath RateDevelopmentDiseaseDisorderDoseDrug KineticsDrug TargetingDrug TherapyDrug resistanceDrug usageDrugsEnzyme GeneEnzymesEthambutolGeneralized GrowthGenomicsGrowthHumanIndazolesIndolesInfectionIsonicotinic Acid HydrazideLeadLiver MicrosomesLung DiseasesM aviumM avium ComplexM intracellulareM tbM tuberculosisM tuberculosis infectionM. aviumM. avium ComplexM. avium intracellulareM. intracellulareM. tbM. tb infectionM. tuberculosisM. tuberculosis infectionM.tb infectionM.tuberculosis infectionMAICMTB infectionMachine LearningMacrolidesMacrophageMedicationMedicinal ChemistryMetabolic StudiesMetabolism StudiesMiceMice MammalsMicrobiologyMinimum Inhibitory Concentration measurementMinimum Inhibitory ConcentrationsModern ManMolecularMolecular InteractionMurineMusMycobacterium aviumMycobacterium avium ComplexMycobacterium avium-intracellulareMycobacterium avium-intracellulare ComplexMycobacterium intracellulareMycobacterium tuberculosisMycobacterium tuberculosis (MTB) infectionMycobacterium tuberculosis infectionMycobutinMycolic AcidMφOralPb elementPharmaceutic ChemistryPharmaceutical AgentPharmaceutical ChemistryPharmaceutical PreparationsPharmaceuticalsPharmacokineticsPharmacologic SubstancePharmacological SubstancePharmacological TreatmentPharmacologyPharmacotherapyPhysiologic AvailabilityPre IND FDA meetingPre-IND mtgPropertyPulmonary DiseasesPulmonary DisorderReactive SiteRegimenResistanceRifabutinRifabutin/MicrobutinRoentgen RaysSiteSolubilityStructureStructure-Activity RelationshipSulfonamidesTB infectionTB therapyTB treatmentTechniquesTestingTherapeuticTissue GrowthToxic effectToxicitiesToxicologyTreatment FailureTuberculosisUnited StatesX-RadiationX-Ray RadiationX-rayXrayamineanalogarabinogalactanbacteria infectionbacterial diseasebiosynthesiscandidate selectionchemical structure functionclinical candidatedesigndesigningdevelopmentaldisease of the lungdisorder of the lungdisseminated TBdisseminated tuberculosisdrug candidatedrug developmentdrug discoverydrug interventiondrug resistantdrug treatmentdrug usedrug/agenteffective therapyeffective treatmentefficacy testingexperienceglobal healthheavy metal Pbheavy metal leadimprovedinfection due to Mycobacterium tuberculosisinhibitorinnovateinnovationinnovativeisoniazidlead optimizationlung disordermachine based learningmachine learning based modelmachine learning modelmetabolic abnormality assessmentmetermodel of animalmortality ratemortality ratiomouse modelmtbmurine modelmycobacterialn-butanenon-tuberculosis mycobacterianon-tuberculosis mycobacterialnon-tuberculous mycobacterianon-tuberculous mycobacterialnontuberculosis mycobacterialnontuberculous mycobacterianontuberculous mycobacterialontogenypathogenpharmaceuticalpharmaceutical interventionpharmacological interventionpharmacological therapypharmacology interventionpharmacology treatmentpharmacotherapeuticspre-IND consultationpre-IND discussionpre-IND meetingpre-Investigational New Drug meetingpre-clinicalpre-clinical developmentpreclinicalpreclinical developmentresistance to Drugresistantresistant to Drugscale upsmall molecular inhibitorsmall molecule inhibitorstructure function relationshipsuccesstherapeutically effectivetherapy failuretreat M. tuberculosistreat Mtbtreat Mycobacterium tuberculosistreat tbtreat tuberculosistuberculosis infectiontuberculosis therapytuberculosis treatmenttuberculous spondyloarthropathy
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ABSTRACT.
Non-tuberculous mycobacteria (NTM) constitute a major threat to global health with over 200,000 annual
cases in the United States alone. Mycobacterium avium complex (MAC) infections are the most common cause
of NTM pulmonary disease, producing a five-year all-cause mortality rate of 25%. M. avium (Mav) accounts for
the majority of MAC…
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