ArticleScientific reports2018
Pharmacological difference between degrader and inhibitor against oncogenic BCR-ABL kinase.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors.Molecular cancer therapeutics · 2025Article
- Exploiting the potential of the ubiquitin-proteasome system in overcoming tyrosine kinase inhibitor resistance in chronic myeloid leukemia.Genes & diseases · 2024Review
- A TRIM21-based bioPROTAC highlights the therapeutic benefit of HuR degradation.Nature communications · 2023Article
- Current Status of Oligonucleotide-Based Protein Degraders.Pharmaceutics · 2023Review
- Targeting the PTP1B-Bcr-Abl1 interaction for the degradation of T315I mutant Bcr-Abl1 in chronic myeloid leukemia.Cancer science · 2023Article
- Androgen and oestrogen receptor co-expression determines the efficacy of hormone receptor-mediated radiosensitisation in breast cancer.British journal of cancer · 2022Article
- Degraders: The Ultimate Weapon Against Amplified Driver Kinases in Cancer.Molecular pharmacology · 2022Review
- Targeted protein degradation: A promise for undruggable proteins.Cell chemical biology · 2021Review
- Development of a Hematopoietic Prostaglandin D Synthase-Degradation Inducer.ACS medicinal chemistry letters · 2021Article
- Deubiquitylase USP25 prevents degradation of BCR-ABL protein and ensures proliferation of Ph-positive leukemia cells.Oncogene · 2020Article
- Selective Degradation of Target Proteins by Chimeric Small-Molecular Drugs, PROTACs and SNIPERs.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Systematic exploration of different E3 ubiquitin ligases: an approach towards potent and selective CDK6 degraders.Chemical science · 2020Article
- Targeted Protein Degradation by Chimeric Compounds using Hydrophobic E3 Ligands and Adamantane Moiety.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Homoharringtonine promotes BCR‑ABL degradation through the p62‑mediated autophagy pathway.Oncology reports · 2020Article
- Design and Characterization of SGK3-PROTAC1, an Isoform Specific SGK3 Kinase PROTAC Degrader.ACS chemical biology · 2019Article
- Targeted protein degradation: elements of PROTAC design.Current opinion in chemical biology · 2019Review
- Targeted Protein Degradation by Chimeric Small Molecules, PROTACs and SNIPERs.Frontiers in chemistry · 2019Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic myelogenous leukemia (CML) is characterized by the oncogenic fusion protein, BCR-ABL protein kinase, against which clinically useful inhibitors have been developed. An alternative approach to treat CML is to degrade the BCR-ABL protein. Recently, potent degraders against BCR-ABL have been developed by conjugating dasatinib to ligands for E3 ubiquitin ligases. Since the degraders contain the dasatinib moiety, they also inhibit BCR-ABL kinase activity, which complicates our understanding of the impact of BCR-ABL degradation by degraders in CML growth inhibition. To address this issue, we chose DAS-IAP, as a potent BCR-ABL degrader, and developed a structurally related inactive degrader, DAS-meIAP, which inhibits kinase activity but does not degrade the BCR-ABL protein. DAS-IAP showed slightly weaker activity than DAS-meIAP in inhibiting cell growth when CML cells were treated for 48 h. However, DAS-IAP showed sustained growth inhibition even when the drug was removed after short-term treatment, whereas CML cell growth rapidly resumed following removal of DAS-meIAP and dasatinib. Consistently, suppression of BCR-ABL levels and downstream kinase signaling were maintained after DAS-IAP removal, whereas kinase signaling rapidly recovered following removal of DAS-meIAP and dasatinib. These results indicate that BCR-ABL degrader shows more sustained inhibition of CML cell growth than ABL kinase inhibitor.
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