Proteomics

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Selectivity profiling of SLC16A3/MCT4 inhibitor slCeMM1 using photoaffinity probe

ABSTRACT: To assess the selectivity of SLC16A3/MCT4 inhibitor slCeMM1, we derived diazirine-alkyne photoaffinity probe (slCeMM1-PAP). We next used HAP1 and MDAMB231 cell lines for MS experiment, comparing the enrichment of proteins by slCeMM1-PAP and conditions where slCeMM1-PAP was competed with slCeMM1 or it’s structurally related inactive control (S1_007). We found that among proteins enriched by slCeMM1-PAP, only SLC16A3 was competed by slCeMM1, but not S1_007, confirming the SLC16A3 engagement by slCeMM1 and suggesting overall good selectivity of slCeMM1.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Leukocyte, Epithelial Cell

DISEASE(S): Acute Leukemia,Breast Cancer

SUBMITTER: Fabian Frommelt  

LAB HEAD: Dr Giulio Superti-Furga

PROVIDER: PXD040089 | Pride | 2023-10-16

REPOSITORIES: Pride

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CC_GSF_169-M1132-F1-F5-P12969-1-OTITOT-TotalPepNorm-SumInd-AR-20221213-V2.mgf Mgf
CC_GSF_169-M1132-F1-F5-P12969-1-OTITOT-TotalPepNorm-SumInd-AR-20221213-V2.mzML Mzml
CC_GSF_169-M1132-F1-F5-P12969-1-OTITOT-TotalPepNorm-SumInd-AR-20221213-V2.mzid.gz Mzid
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CC_GSF_169-M1132-F1-F5-P12969-1-OTITOT-TotalPepNorm-SumInd-AR-20221213-V2.xlsx Xlsx
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Publications

Despite being considered druggable and attractive therapeutic targets, most of the solute carrier (SLC) membrane transporters remain pharmacologically underexploited. One of the reasons for this is a lack of reliable chemical screening assays, made difficult by functional redundancies among SLCs. In this study we leveraged synthetic lethality between the lactate transporters SLC16A1 and SLC16A3 in a screening strategy that we call paralog-dependent isogenic cell assay (PARADISO). The system invo  ...[more]

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