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Heterobifunctional molecules that recruit E3 ubiquitin ligases, such as cereblon, for targeted protein degradation represent an emerging pharmacological strategy. A major unanswered question is how generally applicable this strategy is to all protein targets. In this study, we designed a multi-kinase degrader by conjugating a highly promiscuous kinase inhibitor with a cereblon-binding ligand, and used quantitative proteomics to discover 28 kinases, including BTK, PTK2, PTK2B, FLT3, AURKA, AURKB, TEC, ULK1, ITK, and nine members of the CDK family, as degradable. This set of kinases is only a fraction of the intracellular targets bound by the degrader, demonstrating that successful degradation requires more than target engagement. The results guided us to develop selective degraders for FLT3 and BTK, with potentials to improve disease treatment. Together, this study demonstrates an efficient approach to triage a gene family of interest to identify readily degradable targets for further studies and pre-clinical developments.
Pubmed ID: 29129717 RIS Download
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This unknown targets IgG
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis monoclonal targets Stat1, phospho (Tyr701)
View all literature mentionsThis polyclonal targets ULK1
View all literature mentionsThis monoclonal targets WEE1
View all literature mentionsThis monoclonal targets Vinculin antibody produced in mouse
View all literature mentionsThis monoclonal targets alpha-Tubulin (DM1A) Mouse mAb
View all literature mentionsThis polyclonal targets PTK2B
View all literature mentionsThis monoclonal targets LC3A/B
View all literature mentionsThis monoclonal targets Human Lck
View all literature mentionsThis monoclonal targets Jak2 (D2E12) XP Rabbit mAb
View all literature mentionsThis monoclonal targets JAK1
View all literature mentionsThis monoclonal targets Itk
View all literature mentionsThis recombinant monoclonal targets GAPDH
View all literature mentionsThis polyclonal targets Flt-3/Flk-2 (C-20)
View all literature mentionsThis monoclonal targets Fert2
View all literature mentionsThis monoclonal targets Cdk7 (C-5)
View all literature mentionsThis monoclonal targets CDK2
View all literature mentionsThis monoclonal targets CDK4
View all literature mentionsThis monoclonal targets Btk (D3H5) Rabbit mAb
View all literature mentionsThis polyclonal targets Aurora B/AIM1
View all literature mentionsThis monoclonal targets Aurora A
View all literature mentionsCell line BTI-Tn-5B1-4 is a Spontaneously immortalized cell line with a species of origin Trichoplusia ni (Cabbage looper)
View all literature mentionsCell line HEK293-FT is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line TMD8 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MV4-11 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MOLT-4 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MOLM-14 is a Cancer cell line with a species of origin Homo sapiens (Human)
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