The rise of degrader drugs

M Teng, NS Gray - Cell Chemical Biology, 2023 - cell.com
The cancer genomics revolution has served up a plethora of promising and challenging
targets for the drug discovery community. The field of targeted protein degradation (TPD) …

PROTAC therapy as a new targeted therapy for lung cancer

JW Li, G Zheng, FJ Kaye, L Wu - Molecular therapy, 2023 - cell.com
Despite recent advances in molecular therapeutics, lung cancer is still a leading cause of
cancer deaths. Currently, limited targeted therapy options and acquired drug resistance …

Piperlongumine conjugates induce targeted protein degradation

J Pei, Y Xiao, X Liu, W Hu, A Sobh, Y Yuan, S Zhou… - Cell chemical …, 2023 - cell.com
Proteolysis targeting chimeras (PROTACs) are bifunctional molecules that degrade target
proteins through recruiting E3 ligases. However, their application is limited in part because …

Recent advances in targeted protein degraders as potential therapeutic agents

N Yang, B Kong, Z Zhu, F Huang, L Zhang, T Lu… - Molecular …, 2024 - Springer
Targeted protein degradation (TPD) technology has gradually become widespread in the
past 20 years, which greatly boosts the development of disease treatment. Contrary to small …

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
Purpose The BCL-2 family of anti-apoptotic proteins, BCL-2, BCL-XL and MCL-1, can
mediate survival of some types of cancer. DT2216 is a PROteolysis-TArgeting Chimera …

[HTML][HTML] Bcl-x short-isoform is essential for maintaining homeostasis of multiple tissues

MA Keller, C Huang, A Ivessa, S Singh… - Iscience, 2023 - cell.com
Summary BCL-2-like protein 1 (BCL2L1) is a key component of cell survival and death
mechanisms. Its dysregulation and altered ratio of splicing variants associate with …

Thalidomide derivatives degrade BCL-2 by reprogramming the binding surface of CRBN

J Wang, M Heinz, K Han, VJ Shah… - Cell Reports Physical …, 2024 - cell.com
Recent studies demonstrate that modified thalidomide chemically alters the binding surface
of its binding E3 ligase, CRBN, leading to the degradation of new substrate proteins. In this …

Reciprocal effects of mTOR inhibitors on pro-survival proteins dictate therapeutic responses in tuberous sclerosis complex

MC McNamara, AM Hosios, ME Torrence, T Zhao… - Iscience, 2022 - cell.com
Summary mTORC1 is aberrantly activated in cancer and in the genetic tumor syndrome
tuberous sclerosis complex (TSC), which is caused by loss-of-function mutations in the TSC …

HDAC3 and HDAC8 PROTAC dual degrader reveals roles of histone acetylation in gene regulation

Y Xiao, S Hale, N Awasthee, C Meng, X Zhang… - Cell chemical …, 2023 - cell.com
HDAC3 and HDAC8 have critical biological functions and represent highly sought-after
therapeutic targets. Because histone deacetylases (HDACs) have a very conserved catalytic …