High-Throughput Mass Spectrometry for Hit Identification: Current Landscape and Future Perspectives

McLaren, David G.; Shah, Vinit; Wısnıewskı, Thomas; Ghislain, Lucien P.; Liu, Chang; Zhang, Hui; Saldanha, S. Adrian

doi:10.1177/2472555220980696

Cited by 40 publications

(36 citation statements)

References 132 publications

(152 reference statements)

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“…53,54 As the technology allows very fast screening, it has already found traction in the HTS field with its application to label-free screening of in vitro assays. 13,15,16,55–59…”

Section: Discussionmentioning

confidence: 99%

“…RapidFire) or surface-based MS techniques, such as matrix-assisted laser/desorption ionization (MALDI). 13 MALDI-time of flight (MALDI-TOF) MS is a versatile, label-free technique that has the potential to accelerate HTS of promising drug candidates. [14][15][16] MALDI-TOF MS is tolerant to a number of standard buffer components and has rapidly become popular in the field of HTS drug discovery due to its versatility, requiring very small sample quantities, and minimal sample clean-up.…”

Section: Introductionmentioning

confidence: 99%

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A MALDI-TOF assay identifies nilotinib as an inhibitor of inflammation in acute myeloid leukaemia

Marín-Rubio

Heap

Heunis

et al. 2021

Preprint

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Inflammatory responses are important in cancer, particularly in the context of monocyte-rich aggressive myeloid neoplasm. We developed a label-free cellular phenotypic drug discovery assay to identify anti-inflammatory drugs in human monocytes derived from acute myeloid leukemia (AML), by tracking several biological features ionizing from only 2,500 cells using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry. A proof-of-concept screen showed that the BCR-ABL inhibitor nilotinib, but not the structurally similar imatinib, blocks inflammatory responses. In order to identify the cellular (off-)targets of nilotinib, we performed thermal proteome profiling (TPP) using TMTpro 16plex. Unlike imatinib, nilotinib inhibits p38-alpha (MAPK14) signalling. This inhibition suppressed the expression of inflammatory cytokines, cell adhesion and innate immunity markers in activated human monocytes derived from AML. Thus, our study provides a tool for the discovery of new anti-inflammatory drugs, which could contribute to the treatment of inflammation in myeloid neoplasms and other diseases.

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“…53,54 As the technology allows very fast screening, it has already found traction in the HTS field with its application to label-free screening of in vitro assays. 13,15,16,55–59…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A MALDI-TOF assay identifies nilotinib as an inhibitor of inflammation in acute myeloid leukaemia

Marín-Rubio

Heap

Heunis

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…68–72 Advances in rapid high-throughout mass spectrometric analysis are also leading to label-free analysis. 73,74 However, we believe simple biochemical and cellular assays stand their ground in medicinal chemistry. Their reductionist approach is powerful for making decisions about SAR.…”

Section: Perspectivesmentioning

confidence: 99%

The Impact of Assay Design on Medicinal Chemistry: Case Studies

et al. 2021

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“…Several attempts to fill this technological gap have been reported, from which some have evolved into commercialized products, while others remain experimental for the time being. 3…”

Section: Introductionmentioning

confidence: 99%

Acoustic Ejection Mass Spectrometry: A Fully Automatable Technology for High-Throughput Screening in Drug Discovery

et al. 2021

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High-Throughput Mass Spectrometry for Hit Identification: Current Landscape and Future Perspectives

Cited by 40 publications

References 132 publications

A MALDI-TOF assay identifies nilotinib as an inhibitor of inflammation in acute myeloid leukaemia

A MALDI-TOF assay identifies nilotinib as an inhibitor of inflammation in acute myeloid leukaemia

The Impact of Assay Design on Medicinal Chemistry: Case Studies

Acoustic Ejection Mass Spectrometry: A Fully Automatable Technology for High-Throughput Screening in Drug Discovery

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