2019年12月2日 · To reduce the toxicity of ABT263, we converted it into DT2216, a BCL-XL proteolysis-targeting chimera (PROTAC), that targets BCL-XL to the Von Hippel-Lindau (VHL) E3 ligase for degradation.

2020年7月16日 · We 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.

DIALECTIC’S LEAD CANDIDATE, DT2216, is a novel Antiapoptotic Protein Targeted Degradation (APTaD™) compound that selectively induces cancer cells to degrade B-cell lymphoma extra large, or BCL-XL, stimulating the cells to commit suicide or become more susceptible to chemotherapy. DT2216 is currently in the clinical phase as a single agent ...

2024年11月5日 · The promising efficacy of DT2216, evidenced by reduced cell viability, synergistic effects with AZA, and in vivo activity in CDX mouse model, supports its potential as a therapeutic option for post-MPN sAML.

2019年11月13日 · We found that the combination of DT2216 with ABT199 (a selective BCL-2 inhibitor) could more effectively kill DFTL-28776 TCL cells than either agent alone in cell culture. The effect of the combination treatment on the growth of DFTL-28776 PDX in …

2023年1月2日 · After screening inhibitors of selected tumorigenic pathways, we found that AZD8055 selectively downregulates MCL-1 in SCLC cells and its combination with DT2216 synergistically killed BCL-X L...

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.

2018年11月29日 · DT2216 in combination with ABT199 effectively inhibited tumor growth in H146 xenografts. Collectively, our findings suggest that targeting Bcl-XL using Bcl-XL Syntholytics can selectively kill Bcl-XL-dependent T-ALL cells and various solid tumor cells without causing significant platelet toxicity.

Bcl-XL Proteolysis Targeting Chimera DT2216 is an anti-apoptotic protein B-cell lymphoma-extra large (Bcl-XL) targeted protein degrader, using the proteolysis targeting chimera (PROTAC) technology, with potential pro-apoptotic, immunomodulating and antineoplastic activities.

2022年3月9日 · We assessed the effect of sotorasib alone or in combination with DT2216 (a clinical-stage BCL-X L proteolysis targeting chimera [PROTAC]) on KRAS G12C -mutated NSCLC, CRC and pancreatic cancer (PC) cell lines using MTS cell viability, colony formation and Annexin-V/PI apoptosis assays.