[HTML][HTML] PROTAC-mediated dual degradation of BCL-xL and BCL-2 is a highly effective therapeutic strategy in small-cell lung cancer

S Khan, L Cao, J Wiegand, P Zhang, M Zajac-Kaye… - Cells, 2024 - mdpi.com
BCL-xL and BCL-2 are validated therapeutic targets in small-cell lung cancer (SCLC).
Targeting these proteins with navitoclax (formerly ABT263, a dual BCL-xL/2 inhibitor) …

[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… - Exploration of targeted …, 2020 - ncbi.nlm.nih.gov
Abstract BCL-X L is an anti-apoptotic protein that plays an important role in tumorigenesis,
metastasis, and intrinsic or therapy-induced cancer drug resistance. More recently, BCL-X L …

Discovery of a Novel BCL-XL PROTAC Degrader with Enhanced BCL-2 Inhibition

P Pal, D Thummuri, D Lv, X Liu, P Zhang… - Journal of medicinal …, 2021 - ACS Publications
BCL-XL and BCL-2 are important targets for cancer treatment. BCL-XL specific proteolysis-
targeting chimeras (PROTACs) have been developed to circumvent the on-target platelet …

[HTML][HTML] Co-targeting BCL-XL and BCL-2 by PROTAC 753B eliminates leukemia cells and enhances efficacy of chemotherapy by targeting senescent cells

Y Jia, L Han, CL Ramage, Z Wang, CC Weng… - …, 2023 - ncbi.nlm.nih.gov
Abstract BCL-X L and BCL-2 are key anti-apoptotic proteins and validated cancer targets.
753B is a novel BCL-X L/BCL-2 proteolysis targeting chimera (PROTAC) that targets both …

Discovery of PROTAC BCL-XL degraders as potent anticancer agents with low on-target platelet toxicity

X Zhang, D Thummuri, X Liu, W Hu, P Zhang… - European journal of …, 2020 - Elsevier
Anti-apoptotic protein BCL-X L plays a key role in tumorigenesis and cancer chemotherapy
resistance, rendering it an attractive target for cancer treatment. However, BCL-X L inhibitors …

[HTML][HTML] DT2216, a synthetic proteolytic selectively targeting Bcl-XL for ubiquitination and degradation in tumor cells but not in platelets, is a safer and more potent …

S Khan, X Zhang, D Lv, Y He, P Zhang, X Liu… - Blood, 2018 - Elsevier
The evasion of apoptosis, or programmed cell death, is a hallmark of cancer, which
promotes tumor initiation and progression. The evasion is in part attributable to the over …

Utilizing PROTAC technology to address the on-target platelet toxicity associated with inhibition of BCL-XL

X Zhang, D Thummuri, Y He, X Liu, P Zhang… - Chemical …, 2019 - pubs.rsc.org
BCL-XL, an anti-apoptotic BCL-2 family protein, plays a key role in cancer cell survival.
However, the potential of BCL-XL as an anti-cancer target has been hampered by the on …

[HTML][HTML] Co-targeting BCL-XL and MCL-1 with DT2216 and AZD8055 synergistically inhibit small-cell lung cancer growth without causing on-target toxicities in mice

S Khan, P Kellish, N Connis, D Thummuri… - Cell Death …, 2023 - nature.com
Small-cell lung cancer (SCLC) is an aggressive malignancy with limited therapeutic options.
The dismal prognosis in SCLC is in part associated with an upregulation of BCL-2 family anti …

Discovery of BCL-XL Heterobifunctional Degrader with Potentially Improved Therapeutic Window and Minimal Platelet Toxicity for Hematological Malignancies

Y Xie, W Xing, W Lai, M Tao, L Gu, M Cao, J Diao… - Blood, 2023 - Elsevier
Background In hematologic malignancies, apoptosis evasion promotes tumor
formation/progression and is driven by the overexpression of anti-apoptotic proteins …

A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity

S Khan, X Zhang, D Lv, Q Zhang, Y He, P Zhang… - Nature medicine, 2019 - nature.com
B-cell lymphoma extra large (BCL-XL) is a well-validated cancer target. However, the on-
target and dose-limiting thrombocytopenia limits the use of BCL-XL inhibitors, such as …