Results 111 to 120 of about 14,786 (290)

Small-Molecule Hydrophobic Tagging Induced Degradation of HaloTag Fusion Proteins [PDF]

, 2011
The ability to regulate any protein of interest in living systems with small molecules remains a challenge. We hypothesized that appending a hydrophobic moiety to the surface of a protein would mimic the partially denatured state of the protein, thus ...
Corson, Timothy W., Crews, Craig M, Holley, Scott A, Neklesa, Taavi K, Raina, Kanak, Schneekloth, Ashley R, Stulberg, Michael J, Sundberg, Thomas B, Tae, Hyun Seop   +8 more
core   +1 more source

Revisiting Target‐Aware de novo Molecular Generation with TarPass: Between Rational Design and Texas Sharpshooter

Advanced Science, EarlyView.
TarPass provides a rigorous benchmark for target‐aware de novo molecular generation by jointly evaluating protein‐ligand interactions, molecular plausibility, and drug‐likeness on 18 well‐studied targets. Results show that current models often fail to consistently surpass random baseline in target‐specific enrichment, while post hoc multi‐tier virtual ...
Rui Qin, Zijie Chen, Yurong Li, Meijing Fang, Longji Shen, Yilong Su, Odin Zhang, Qinghan Wang, Qun Su, Jike Wang, Tingjun Hou, Yu Kang   +11 more
wiley   +1 more source

Chemotherapy‐Enabled Colorectal Cancer Immunotherapy of Self‐Delivery Nano‐PROTACs by Inhibiting Tumor Glycolysis and Avoiding Adaptive Immune Resistance

Advancement of science
The chemo‐regulation abilities of chemotherapeutic medications are appealing to address the low immunogenicity, immunosuppressive lactate microenvironment, and adaptive immune resistance of colorectal cancer.
Linping Zhao, Rongrong Zheng, Xiaona Rao, Chu‐Yu Huang, Hangyu Zhou, Xi-Yong Yu, Xue-yan Jiang, Shiying Li   +7 more
semanticscholar   +1 more source

“Membrane‐Guided” Repair Strategy: Precision Delivery of GGT1 Degrader for Targeted Repair and Regeneration of Spinal Cord Neurons

Advanced Science, EarlyView.
This study confirms that GGT1 is a key driver of neuronal ferroptosis following spinal cord injury. We developed NSCm@EA, a biomimetic delivery system coated with neural stem cell membranes, for precise delivery of enocyanin to injured neurons. By combining targeted delivery with ubiquitination degradation mechanisms, this system promotes MGRN1 ...
Tao Yang, Lei Ye, Peigen Xie, Tao Song, Jian Chen, Heng Zhao, Zhengshan Liu, Xi Chen, Jianing Ding, Xintian Ding, Ao Shao, Miaomiao Wu, Fengdong Zhao, Siyue Tao, Tao You   +14 more
wiley   +1 more source

T‐Cell Exhaustion in the Tumor Microenvironment: Subcellular Dysfunction, Pan‐Cancer Characteristics, and Therapeutic Interventions

Advanced Science, EarlyView.
This study elucidates the mechanisms of subcellular multidimensional collapse in exhausted T cells. By specifically targeting the nucleus, mitochondria, and endoplasmic reticulum, strategic interventions can effectively remodel the compromised organelle network. This integrated approach drives comprehensive T cell resuscitation, ultimately establishing
Mingxing Wang, Wanhui Dong, Jian Chen, Zhangjie Zhou, Shujuan Fu, Tingting Wu, Haiyan Jiang, Zhiying Wang, Zhixian Zhong, Yi Zhong   +9 more
wiley   +1 more source

Proteasome Inhibitors: Harnessing Proteostasis to Combat Disease [PDF]

, 2020
The proteasome is the central component of the main cellular protein degradation pathway. During the past four decades, the critical function of the proteasome in numerous physiological processes has been revealed, and proteasome activity has been linked
Li, Jing, Sherman, David J.
core  

Exploring the chemical space of orally bioavailable PROTACs.

Drug Discovery Today
A principal challenge in the discovery of proteolysis targeting chimeras (PROTACs) as oral medications is their bioavailability. To facilitate drug design, it is therefore essential to identify the chemical space where orally bioavailable PROTACs are ...
Giulia Apprato, Vasanthanathan Poongavanam, Diego García Jiménez, Yoseph Atilaw, M. Erdélyi, G. Ermondi, G. Caron, Jan Kihlberg   +7 more
semanticscholar   +1 more source

Effect of carbamazepine on the pharmacokinetics of vepdegestrant, a PROteolysis TArgeting Chimera estrogen receptor degrader, in healthy adults

British Journal of Clinical Pharmacology, EarlyView.
Aim To evaluate the effects of carbamazepine, a strong cytochrome P450 (CYP)3A4 inducer, on the pharmacokinetics and safety of vepdegestrant, a PROteolysis TArgeting Chimera estrogen receptor degrader. Methods This was a phase 1, open‐label, fixed‐sequence, two‐period study in healthy adult participants.
Hechuan Wang, Jennifer A. Winton, Kyle T. Matschke, Alexandre Stouffs, Kimberly C. Lee, Yuanyuan Zhang, Wenlian Qiao, Weiwei Tan   +7 more
wiley   +1 more source

SLUG transcription factor : a pro-survival and prognostic factor in gastrointestinal stromal tumour [PDF]

, 2017
Background: The SLUG transcription factor has been linked with the KIT signalling pathway that is important for gastrointestinal stromal tumour (GIST) tumourigenesis. Its clinical significance in GIST is unknown.
A Catalano, Aki Vehtari, AM Haslehurst, B Motro, B Nilsson, B Nilsson, Bengt Nilsson, C Bermejo-Rodriguez, C Cobaleda, C Tribulo, CD Fletcher, DA Tuveson, DW Wu, E Wardelmann, Eva Wardelmann, F Ducimetiere, GD Demetri, H Joensuu, H Joensuu, H Joensuu, H Joensuu, Harri Sihto, Heikki Joensuu, HW Yang, J Andersson, J Perez-Losada, J Perez-Losada, J Qian, K Zhang, K Zhang, Kirsten Sundby Hall, M Emadi Baygi, M Mancini, M Nannini, M Sanchez-Martin, M Shioiri, MA Nieto, Maarit Sarlomo-Rikala, MC Heinrich, MC Heinrich, Mikael Eriksson, NK Kurrey, Olli-Pekka Pulkka, Peter Reichardt, R Vitali, RA Spritz, RJ Deshaies, RP Dematteo, S Bauer, S Hirota, S Kim, W Zhou, WS Wu, Y Uchikado, Y Wang   +54 more
core   +1 more source

PROTACs: Current and Future Potential as a Precision Medicine Strategy to Combat Cancer

Molecular Cancer Therapeutics
Proteolysis targeting chimeras (PROTAC) are an emerging precision medicine strategy, which targets key proteins for proteolytic degradation to ultimately induce cancer cell killing.
Kailee A. Rutherford, K. McManus
semanticscholar   +1 more source