ArticleJournal of hematology & oncology2020
DT2216-a Bcl-xL-specific degrader is highly active against Bcl-xL-dependent T cell lymphomas.
Article in Journal of hematology & oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 125 citations in OpenAlex.
- Targeted degradation of protein in hematologic malignancies: mechanisms, therapeutic strategies, and clinical prospects.Cancer gene therapy · 2026Review
- De Novo-Designed Bifunctional Proteins for Targeted Protein Degradation.Journal of the American Chemical Society · 2026Article
- Proteolysis Targeting Chimeric-Based Technology in Myeloma and Lymphoma.Molecular cancer therapeutics · 2026Review
- Review
- Carborane Hydrophobic Tags Drive Selective Degradation of Endogenous KRASACS bio & med chem Au · 2026Article
- From Platelet Toxicity to Precision Targeting: Evolving Strategies to Overcome Thrombocytopenia in BCL-2/BCL-XL Inhibition.Health science reports · 2026Article
- The Combination of a BCL-xL PROTAC and an mTOR Inhibitor Sensitizes Pancreatic Ductal Adenocarcinoma to KRASCancers · 2026Article
- Targeting BCL-XL for degradation synergizes with gemcitabine against cholangiocarcinoma.BMC medicine · 2026Article
- PROTAC-mediated degradation of Bcl-xL potentiates target therapy in preclinical melanoma models.Journal of experimental & clinical cancer research : CR · 2026Article
- The combination of BCL-xL PROTAC and mTOR inhibitor sensitizes pancreatic ductal adenocarcinoma to KRASbioRxiv : the preprint server for biology · 2026Article
- BCL-XL drives fibrotic and leukemic progression in myeloproliferative neoplasms.Frontiers in immunology · 2026Article
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- Developing therapeutic strategies to target MCL1 and BCLXL in lethal prostate cancer.iScience · 2025Article
- Context Matters: E3 Ligase-Ligand Pairing Strategies for Optimized PROTAC Performance.Protein & cell · 2025Article
- Ion channel inhibition by targeted recruitment of NEDD4-2 with divalent nanobodies.Nature communications · 2025Article
- Next-Generation Proteolysis-Targeting Chimeras in Precision Oncology: Multifunctional Designs, Emerging Modalities, and Translational Prospects in Targeted Protein Degradation.Drug development research · 2025Review
- Article
- Review
- Targeted protein degradation with small molecules for cancer immunotherapy.Asian journal of pharmaceutical sciences · 2025Review
- Discovery of XZ338, a highly potent BCL-XEuropean journal of medicinal chemistry · 2025Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundPatients with advanced T cell lymphomas (TCLs) have limited therapeutic options and poor outcomes in part because their TCLs evade apoptosis through upregulation of anti-apoptotic Bcl-2 proteins. Subsets of TCL cell lines, patient-derived xenografts (PDXs), and primary patient samples depend on Bcl-xL for survival. However, small molecule Bcl-xL inhibitors such as ABT263 have failed during clinical development due to on-target and dose-limiting thrombocytopenia.
methodsWe have developed DT2216, a proteolysis targeting chimera (PROTAC) targeting Bcl-xL for degradation via Von Hippel-Lindau (VHL) E3 ligase, and shown that it has better anti-tumor activity but is less toxic to platelets compared to ABT263. Here, we examined the therapeutic potential of DT2216 for TCLs via testing its anti-TCL activity in vitro using MTS assay, immunoblotting, and flow cytometry and anti-TCL activity in vivo using TCL cell xenograft and PDX model in mice.
resultsThe results showed that DT2216 selectively killed various Bcl-xL-dependent TCL cells including MyLa cells in vitro. In vivo, DT2216 alone was highly effective against MyLa TCL xenografts in mice without causing significant thrombocytopenia or other toxicity. Furthermore, DT2216 combined with ABT199 (a selective Bcl-2 inhibitor) synergistically reduced disease burden and improved survival in a TCL PDX mouse model dependent on both Bcl-2 and Bcl-xL.
conclusionsThese findings support the clinical testing of DT2216 in patients with Bcl-xL-dependent TCLs, both as a single agent and in rational combinations.
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Registered trials
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.