ArticleLeukemia2011
Chemoproteomics-based kinome profiling and target deconvolution of clinical multi-kinase inhibitors in primary chronic lymphocytic leukemia cells.
Article in Leukemia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 75 citations in OpenAlex.
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- Insights into the structural and functional activities of forgotten Kinases: PCTAIREs CDKs.Molecular cancer · 2024Review
- Kinobead Profiling Reveals Reprogramming of BCR Signaling in Response to Therapy within Primary CLL Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Affinity-based profiling of endogenous phosphoprotein phosphatases by mass spectrometry.Nature protocols · 2021Review
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- CDK inhibitors in cancer therapy, an overview of recent development.American journal of cancer research · 2021Review
- Chemical proteomics reveals target selectivity of clinical Jak inhibitors in human primary cells.Scientific reports · 2019Article
- Systematic analysis of protein turnover in primary cells.Nature communications · 2018Article
- Defining a therapeutic window for kinase inhibitors in leukemia to avoid neutropenia.Oncotarget · 2017Article
- Monitoring Cell-surfaceMolecular & cellular proteomics : MCP · 2017Article
- ABCB1 as predominant resistance mechanism in cells with acquired SNS-032 resistance.Oncotarget · 2016Article
- Global discovery of protein kinases and other nucleotide-binding proteins by mass spectrometry.Mass spectrometry reviews · 2016Review
- Functional interdependence of BRD4 and DOT1L in MLL leukemia.Nature structural & molecular biology · 2016Article
- Thermal proteome profiling monitors ligand interactions with cellular membrane proteins.Nature methods · 2015Article
- Thermal proteome profiling for unbiased identification of direct and indirect drug targets using multiplexed quantitative mass spectrometry.Nature protocols · 2015Article
- Catalytic in vivo protein knockdown by small-molecule PROTACs.Nature chemical biology · 2015Article
- A novel Cdk9 inhibitor preferentially targets tumor cells and synergizes with fludarabine.Oncotarget · 2014Article
- Testing of SNS-032 in a Panel of Human Neuroblastoma Cell Lines with Acquired Resistance to a Broad Range of Drugs.Translational oncology · 2013Article
- Cyclin-dependent kinase inhibitor therapy for hematologic malignancies.Expert opinion on investigational drugs · 2013Review
- Chemical proteomic analysis reveals the drugability of the kinome of Trypanosoma brucei.ACS chemical biology · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pharmacological induction of apoptosis in neoplastic B cells presents a promising therapeutic avenue for the treatment of chronic lymphocytic leukemia (CLL). We profiled a panel of clinical multi-kinase inhibitors for their ability to induce apoptosis in primary CLL cells. Whereas inhibitors targeting a large number of receptor and intracellular tyrosine kinases including c-KIT, FLT3, BTK and SYK were comparatively inactive, the CDK inhibitors BMS-387032 and flavopiridol showed marked efficacy similar to staurosporine. Using the kinobeads proteomics method, kinase expression profiles and binding profiles of the inhibitors to target protein complexes were quantitatively monitored in CLL cells. The targets most potently affected were CDK9, cyclin T1, AFF3/4 and MLLT1, which may represent four subunits of a deregulated positive transcriptional elongation factor (p-TEFb) complex. Albeit with lower potency, both drugs also bound the basal transcription factor BTF2/TFIIH containing CDK7. Staurosporine and geldanamycin do not affect these targets and thus seem to exhibit a different mechanism of action. The data support a critical role of p-TEFb inhibitors in CLL that supports their future clinical development.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.