[HTML][HTML] DT2216—a Bcl-xL-specific degrader is highly active against Bcl-xL-dependent T cell lymphomas

Y He, R Koch, V Budamagunta, P Zhang… - Journal of hematology & …, 2020 - Springer
… (PROTAC) targeting Bcl-xL for degradation via Von Hippel-Lindau (VHL) E3 ligase, and
shown that it has better anti-tumor activity … cannot be achieved by the use of either Bcl-xl-specific …

[HTML][HTML] Targeting anti-apoptotic BCL-2 family proteins for cancer treatment

X Zhang, X Liu, D Zhou, G Zheng - Future Medicinal Chemistry, 2020 - Future Science
… platelets, have been recruited to degrade BCL-X L [13,… PROTAC degraders. Further, the
lead candidate, DT2216, a VHL-based PROTAC derived from ABT-263, achieved better potency

[HTML][HTML] BCL-XL PROTAC degrader DT2216 synergizes with sotorasib in preclinical models of KRASG12C-mutated cancers

S Khan, J Wiegand, P Zhang, W Hu… - Journal of Hematology & …, 2022 - Springer
… BCL-X L proteolysis targeting chimera [PROTAC]) on KRAS G12C -mutated NSCLC, …
antitumor efficacy of sotorasib in vivo. Collectively, our findings suggest that due to cytostatic activity

Discovery of IAP-recruiting BCL-XL PROTACs as potent degraders across multiple cancer cell lines

X Zhang, Y He, P Zhang, V Budamagunta, D Lv… - European journal of …, 2020 - Elsevier
… importance of selecting suitable E3 members to achieve effective cellular activity. … degrade
BCL-X L and kill various cancer cells [[14], [15], [16]]. PROTAC 8a has similar cell killing effect

[HTML][HTML] The PROTAC selectively degrading Bcl-xL represents a novel Hedgehog pathway inhibitor with capacity of combating resistance to Smoothened inhibitors …

S Zhang, Y Chen, Z Xu, J Yang, R Sun, J Wang… - Theranostics, 2022 - ncbi.nlm.nih.gov
… -225, pediatric patients whose bones have not achieved full maturity were found to develop
… Furthermore, we found that the potent antitumor activity of SIAIS316034 corresponded well …

[HTML][HTML] PROTACs are effective in addressing the platelet toxicity associated with BCL-XL inhibitors

P Zhang, X Zhang, X Liu, S Khan, D Zhou… - … of targeted anti-tumor …, 2020 - ncbi.nlm.nih.gov
… These findings demonstrated the potentially broad utility of PROTAC technology to achieve
… in a unique mechanism of action (MOA). In brief, once the PROTAC degrader enters the cell, …

Resistance to the BCL-XL degrader DT2216 in T-cell acute lymphoblastic leukemia is rare and correlates with decreased BCL-XL proteolysis

A Jaiswal, A Jaiswal, EA Williamson, J Gelfond… - Cancer chemotherapy …, 2023 - Springer
… -targeting chimera (PROTAC), DT2216 as a specific BCL-XL protein degrader [6,7,8]. … of
DT2216 that exceeded what we reported could be achieved within a T-ALL xenografted tumor in …

Mivebresib synergized with PZ703b, a novel Bcl-xl PROTAC degrader, induces apoptosis in bladder cancer cells via the mitochondrial pathway

Y Xu, Z Lei, J Zhu, L Wan - Biochemical and Biophysical Research …, 2022 - Elsevier
… of Bcl-xl could confer can cells resistance against BET inhibitors [5], we hypothesized that
Bcl-xl PROTAC, when combined with BET inhibitors, may increase their anti-tumor effects. To …

Trends in targeting Bcl-2 anti-apoptotic proteins for cancer treatment

Z Zhang, L Bai, L Hou, H Deng, S Luan, D Liu… - European Journal of …, 2022 - Elsevier
… not only to achieve strong antitumor activity but also mitigate … Highlighting the advantages
of PROTAC over conventional … The crystallographic information reveals that this degrader not …

[HTML][HTML] Proteolysis-targeting chimera against BCL-XL destroys tumor-infiltrating regulatory T cells

R Kolb, U De, S Khan, Y Luo, MC Kim, H Yu… - Nature …, 2021 - nature.com
… -X L degrader—a proteolysis-targeting chimera (PROTAC) referred to … We also developed
another similar PROTAC PZ15227 that … This can be achieved pharmacologically by applying …