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PXD040208-2

PXD040208 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleKinase Selectivity Profiling of anti-MRSA Diarylimidazoles in HEK293 Cells
DescriptionAntimicrobial resistance (AMR) is widely acknowledged as one of the most serious public health threats facing the world, yet the private sector finds it challenging to generate much-needed medicines. As an alternative discovery approach, a small array of diarylimidazoles was screened against the ESKAPE pathogens and the results made publicly available through the Open Source Antibiotics (OSA) consortium. Of the 18 compounds tested (at 32 μg/mL), 15 showed >90% growth inhibition activity against MRSA alone. In the subsequent hit-to-lead optimization of this chemotype, 147 new heterocyclic compounds containing the diarylimidazole and other core motifs were synthesized, tested against MRSA and structure-activity relationships identified. While potent, these compounds have moderate to high clearance rates and some associated toxicity. The best overall balance of parameters was found with OSA_975, a compound with good potency and solubility and slow clearance in rat hepatocytes. In this study, we used multiplexed kinase inhibitor beads/mass spectrometry (MIB/MS) to study the human molecular targets of these phenotypically active compounds.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:26:01.069.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAurora Cabrera
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-02-16 14:54:23ID requested
12024-01-26 07:19:57announced
22024-10-22 06:26:02announced2024-10-22: Updated project metadata.
Publication List
10.1021/acsinfecdis.3c00286;
Klug DM, Tse EG, Silva DG, Cao Y, Charman SA, Chauhan J, Crighton E, Dichiara M, Drake C, Drewry D, da Silva Emery F, Ferrins L, Graves L, Hopkins E, Kresina TAC, Lorente-Mac, í, as Á, Perry B, Phipps R, Quiroga B, Quotadamo A, Sabatino GN, Sama A, Sch, ä, tzlein A, Simpson QJ, Steele J, Shanu-Wilson J, Sj, ö P, Stapleton P, Swain CJ, Vaideanu A, Xie H, Zuercher W, Todd MH, . ACS Infect Dis, 9(12):2423-2435(2023) [pubmed]
Keyword List
submitter keyword: diarylimidazole, MIB-MS, kinases, HEK293, antimicrobials
Contact List
Matthew H. Todd
contact affiliationSchool of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX
contact emailmatthew.todd@ucl.ac.uk
lab head
Aurora Cabrera
contact affiliationDepartment of Pharmacology at UNC Chapel Hill
contact emailAurora_Cabrera@med.unc.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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