2019
DOI: 10.1038/s41591-019-0668-z
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Abstract: Z. are inventors of two pending patent applications for use of BCL-X L PROTACs as senolytic and antitumor agents. R.H., G.Z., and D.Z. are co-founders of and have equity in Dialectic Therapeutics, which develops BCL-X L PROTACs to treat cancer.

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Cited by 352 publications
(386 citation statements)
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“…We also show that Nav‐Gal reduces apoptosis in platelets, using both human and mouse blood samples. A recent study has shown that another Navitoclax derivative, namely DT2216, exerts anti‐tumour activity by targeting BCL‐ X L to the VHL E3 ligase for proteolytic degradation (Khan et al, 2019). However, distinctly to Nav‐Gal, DT2216 has not been designed for targeting senescent cells, but for reducing thrombocytopenia (as platelets are characterized by poor VHL E3 ligase expression) while maintaining anti‐cancer properties.…”
Section: Discussionmentioning
confidence: 99%
“…We also show that Nav‐Gal reduces apoptosis in platelets, using both human and mouse blood samples. A recent study has shown that another Navitoclax derivative, namely DT2216, exerts anti‐tumour activity by targeting BCL‐ X L to the VHL E3 ligase for proteolytic degradation (Khan et al, 2019). However, distinctly to Nav‐Gal, DT2216 has not been designed for targeting senescent cells, but for reducing thrombocytopenia (as platelets are characterized by poor VHL E3 ligase expression) while maintaining anti‐cancer properties.…”
Section: Discussionmentioning
confidence: 99%
“…Because VHL expression is low in platelets, DT2216 was less toxic to platelets. DTT2216 showed in vitro and in vivo efficacy in various preclinical models of hematological malignancies [110].…”
Section: Selective Inhibitors Of Mcl-1 and Bcl-xl Inhibitors In Chronmentioning
confidence: 99%
“…Thus, cell/tissue specificity could be achieved by converting an inhibitor to a PROTAC. In proof of concept studies, both Von Hippel-Lindau (VHL) cullin-2 and cereblon (CRBN) cullin-4A RING E3 ligases, which were found to be minimally expressed in human platelets, have been recruited to degrade BCL-X L [13,14]. The preliminary data support the reduction of on-target platelet toxicity for both CRBN-based and VHL-based PROTAC degraders.…”
Section: Ongoing Strategies In Targeting Bcl-x Lmentioning
confidence: 79%