Results 51 to 60 of about 5,184,182 (156)

P-NADs: PUX-based NAnobody degraders for ubiquitin-independent degradation of target proteins

Heliyon
Targeted protein degradation (TPD) allows cells to maintain a functional proteome and to rapidly adapt to changing conditions. Methods that repurpose TPD for the deactivation of specific proteins have demonstrated significant potential in therapeutic and
Jun Wang, Georgy Chistov, Junrui Zhang, Brandon Huntington, Israa Salem, Anandsukeerthi Sandholu, Stefan T. Arold   +6 more
doaj   +1 more source

A Plug‐and‐Play Platform for Customizing Multivalent Degraders and Degrader‐Drug Conjugates

Advanced Science
Traditional targeted protein degradation (TPD) strategies are largely ineffective against membrane proteins, which constitute over 60% of drug targets. To address this, we develop a modular “plug‐and‐play” UPTAB (Ultrahigh‐affinity Protein pairs fused to
Mengqing Zhao, Yan Deng, Jianjian Han, Yong Xie, Kai Bao, Lixin Ma, Lilong Liu, Wuxiang Mao   +7 more
doaj   +1 more source

Targeted protein degradation in cancers: Orthodox PROTACs and beyond

The Innovation, 2023
Targeted protein degradation (TPD) is emerging as a strategy to overcome the limitations of traditional small-molecule inhibitors. Proteolysis-targeting chimera (PROTAC) technology can be used to target proteins by hijacking the ubiquitin-proteasome ...
Jin Li, Xinxin Chen, Aiping Lu, Chao Liang   +3 more
doaj   +1 more source

A Versatile DNA‐Encoded Library Platform for the Discovery of Highly Cooperative Chemical Inducers of Proximity

Advanced Science, EarlyView.
We present a versatile DNA‐encoded library (DEL) platform designed for rapid library synthesis and subsequent screening for chemical inducers of proximity (CIPs) across various presenter proteins of choice. Applying this approach, we discovered a novel molecular glue‐like compound mediating CRBN‐BRD9 ternary complex formation with remarkable ...
Bingqi Tong, Sunny A. Tang, Yifan Deng, Zhihan Nan, Alison X. Gao, Gregory A. Michaud, Simone Bonazzi, Frédéric Berst, Frédéric J. Zécri, Shuang Liu, William J. Gibson, Stuart L. Schreiber   +11 more
wiley   +1 more source

Bimodular architecture of bacterial effector SAP05 that drives ubiquitin-independent targeted protein degradation [PDF]

, 2023
In eukaryotes, targeted protein degradation (TPD) typically depends on a series of interactions among ubiquitin ligases that transfer ubiquitin molecules to substrates leading to degradation by the 26S proteasome.
Kamoun, Sophien, Hogenhout, Saskia A., Mirkin, Federico G., Liu, Qun, Huang, Weijie, Singh, Yeshveer, Maqbool, Abbas, Stevenson, Clare E. M., Lawson, David M.   +8 more
core   +1 more source

Targeted protein degradation: mechanisms, strategies and application

Signal Transduction and Targeted Therapy, 2022
Traditional drug discovery mainly focuses on direct regulation of protein activity. The development and application of protein activity modulators, particularly inhibitors, has been the mainstream in drug development.
Lin Zhao, Jia Zhao, Kunhong Zhong, Aiping Tong, Da Jia   +4 more
doaj   +1 more source

Degrading GPX4 via Biomimetic Nanoparticle‐Mediated In Situ Synthesis of Deep‐Learning‐Designed Binder‐Degron Chimeras for Prostate Cancer Therapy

Advanced Science, EarlyView.
A deep‐learning‐designed binder is fused to a combinatorial degron to create a binder‐degron chimera (bdC) that recruits the CUL2‐RING ubiquitin ligase complex. Encapsulation in a prostate‐cancer‐targeted, CD47‐camouflaged nanocarrier enables tumor‐specific in situ bdC expression, triggering GPX4 degradation and ferroptosis, thereby establishing a ...
Si‐Han Zhang, Ye An, Na Zeng, Mei‐Cheng Liu, Jian‐Xuan Sun, Xi Gong, Jin‐Zhou Xu, Shao‐Gang Wang, Qi‐Dong Xia   +8 more
wiley   +1 more source

AI‐Designed TREM1‐Targeted LYTAC Nanoparticles Reprogram the Neuroimmune Microenvironment in Traumatic Brain Injury

Advanced Science, EarlyView.
AI‐enabled de novo design of a TREM1 binder, integrated into a BBB‐crossing and macrophage‐targeted nanoplatform, enables TREM1 degradation and attenuates neuroinflammation, thereby promoting neuroprotection and tissue repair after traumatic brain injury. ABSTRACT Secondary neuroinflammation drives progressive damage after traumatic brain injury (TBI),
Yimin Huang, Yuan Liu, Huan Peng, Yu Ni, Zhengqiao Jiang, Chenxuan Yu, Xincheng Zhang, Huayu Kang, Yanchao Liu, Juan Chen, Kai Zhao, Lin Han, Xin Zou, Kai Shu, Xiaochuan Wang, Jian‐Zhi Wang, Ting Lei, Chao Gan, Jianfeng Liu, Huaqiu Zhang   +19 more
wiley   +1 more source

Multiple C-terminal Lysine residues target p53 for ubiquitin-proteasome-mediated degradation [PDF]

, 2000
This work was supported by the Medical Research Council, the Biotechnology and Biological Research Council, and the Cancer Research Campaign. D.P.L. is a Gibb fellow of the Cancer Research Campaign.In normal cells, p53 is maintained at a low level by ...
Lain, Sonia, Lane, David P., T. Hay, Ronald, Hay, Ronald Thomas, Rodriguez, Manuel S, Desterro, Joana M P   +6 more
core   +1 more source

Lenalidomide derivatives and proteolysis-targeting chimeras for controlling neosubstrate degradation

Nature Communications, 2023
Lenalidomide, an immunomodulatory drug (IMiD), is commonly used as a first-line therapy in many haematological cancers, such as multiple myeloma (MM) and 5q myelodysplastic syndromes (5q MDS), and it functions as a molecular glue for the protein ...
Satoshi Yamanaka, Hirotake Furihata, Yuta Yanagihara, Akihito Taya, Takato Nagasaka, Mai Usui, Koya Nagaoka, Yuki Shoya, Kohei Nishino, Shuhei Yoshida, Hidetaka Kosako, Masaru Tanokura, Takuya Miyakawa, Yuuki Imai, Norio Shibata, Tatsuya Sawasaki   +15 more
doaj   +1 more source