Structural insights into PROTAC-mediated degradation of Bcl-xL

C Chung, H Dai, E Fernandez, CP Tinworth… - ACS Chemical …, 2020 - ACS Publications
The Bcl-2 family of proteins, such as Bcl-xL and Bcl-2, play key roles in cancer cell survival.
Structural studies of Bcl-xL formed the foundation for the development of the first Bcl-2 family …

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 …

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 …

Development of a BCL-xL and BCL-2 dual degrader with improved anti-leukemic activity

D Lv, P Pal, X Liu, Y Jia, D Thummuri, P Zhang… - Nature …, 2021 - nature.com
Abstract PROteolysis-TArgeting Chimeras (PROTACs) have emerged as an innovative drug
development platform. However, most PROTACs have been generated empirically because …

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
Abstract Targeting BCL-X L via PROTACs is a promising strategy in reducing BCL-X L
inhibition associated platelet toxicity. Recently, we reported potent BCL-X L PROTAC …

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 …

PROTAC-mediated crosstalk between E3 ligases

C Steinebach, H Kehm, S Lindner, LP Vu… - Chemical …, 2019 - pubs.rsc.org
Small-molecule heterobifunctional degraders can effectively control protein levels and are
useful research tools. We assembled proteolysis targeting chimeras (PROTACs) from a …

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 …

Structural basis of PROTAC cooperative recognition for selective protein degradation

MS Gadd, A Testa, X Lucas, KH Chan, W Chen… - Nature chemical …, 2017 - nature.com
Inducing macromolecular interactions with small molecules to activate cellular signaling is a
challenging goal. PROTACs (proteolysis-targeting chimeras) are bifunctional molecules that …

Structure-guided design of a selective BCL-XL inhibitor

G Lessene, PE Czabotar, BE Sleebs, K Zobel… - Nature chemical …, 2013 - nature.com
The prosurvival BCL-2 family protein BCL-X L is often overexpressed in solid tumors and
renders malignant tumor cells resistant to anticancer therapeutics. Enhancing apoptotic …