Results 111 to 120 of about 8,212 (230)

Recent progress on the development of hydrogel‐based microneedles for transdermal drug delivery

VIEW, EarlyView.
This study provides a comprehensive and up‐to‐date analysis of recent progress in HMN technology, covering fundamental transdermal delivery mechanisms and design principles, biomaterials used in HMN fabrication, drug loading and release strategies, and emerging therapeutic applications.
Mohammad Muhtasim Ittisaf, Salman Farsi Taharat, Md. Sadek Miah, Hasan Tasnim Salehin, M. Azam Ali, Shoeb Ahmed   +5 more
wiley   +1 more source

Targeting protein–protein interactions with reversible covalent modalities: Non‐cysteine chemistries

British Journal of Pharmacology, EarlyView.
Abstract Protein–protein interactions (PPIs) are central to diverse cellular functions, and represent a rapidly expanding class of therapeutic targets. Advancements in covalent drug design have enabled small‐molecule drugs to overcome challenges associated with engaging these targets, such as limited durations of action and difficult‐to‐drug (expansive,
Ruchira Basu, Steven Fletcher
wiley   +1 more source

Data-driven Design of PROTAC Linkers to Improve PROTAC Cell Membrane Permeability

JACS Au
Proteolysis-targeting chimeras (PROTACs) are promising next-generation therapeutics for the degradation of disease-associated proteins. However, optimizing the physicochemical properties of PROTACs, particularly their poor cell mem-brane permeability, remains challenging.
Yuki Murakami, Shoichi Ishida, Nobuo Cho, Hitomi Yuki, Masateru Ohta, Teruki Honma, Yosuke Demizu, Kei Terayama   +7 more
openaire   +2 more sources

A lipid nanoparticle-based peptide-proteolysis-targeting chimera degrades BCL6 for diffuse large B-cell lymphoma treatment

Discover Oncology
B-cell lymphoma 6 (BCL6) is an attractive drug target for diffuse large B-cell lymphoma (DLBCL). This study aimed to create a lipid nanoparticle (LNP)-based peptide-proteolysis-targeting chimera (PROTAC), specifically BCL6-PROTAC, to develop effective ...
Shiwei Liu, Xueying Gao, Xuan Ye, Yi Chen, Kai Wang, Yangsui Liu, Sanmei Wang, Haorui Shen, Hongyu Shen, Ran Li, Xiaoyan Qu, Lei Fan   +11 more
doaj   +1 more source

Peripheral targets for neuropathic pain

British Journal of Pharmacology, EarlyView.
Neuropathic pain represents a significant clinical challenge, with still limited pharmacological approaches to symptomatic relief. This review focuses on molecular targets implicated in neuropathic pain, particularly those involved in peripheral mechanisms. Using the IUPHAR/BPS database of biological targets, their occurrence together with ‘neuropathic
Amirhossein Afsharipour, Cosmin I. Ciotu, Felix J. Resch, Michael J. M. Fischer   +3 more
wiley   +1 more source

The c‐Src inhibitor eCF506 diminishes opioid tolerance and reduces β‐arrestin2 recruitment

British Journal of Pharmacology, EarlyView.
Morphine activation of μ receptors causes tolerance through c‐Src activation and β‐arrestin2 recruitment. c‐Src inhibition or degradation reduces β‐arrestin2 recruitment, μ receptor endocytosis, while causing receptor upregulation, all likely contributing to reduced morphine tolerance.
Samuel Singleton, Fraser Nunn, Erika Lace, Álvaro Lorente‐Macías, Rachel Toth, Asier Unciti‐Broceta, Tim G. Hales   +6 more
wiley   +1 more source

Characterization of PROTAC specificity and endogenous protein interactomes using ProtacID

Nature Communications
Here we describe ProtacID, a flexible BioID (proximity-dependent biotinylation)-based approach to identify PROTAC-proximal proteins in living cells. ProtacID analysis of VHL- and CRBN-recruiting PROTACs targeting a number of different proteins (localized
Suman Shrestha, Matthew E. R. Maitland, Laili Jing, Shili Duan, David Y. Nie, Jonathan St-Germain, Michael Kanaris, Dalia Barsyte-Lovejoy, Cheryl H. Arrowsmith, Brian Raught   +9 more
doaj   +1 more source

Daraxonrasib and Beyond: Pan‐RAS Inhibition, Resistance, and Next‐Generation Strategies

Cancer Science, EarlyView.
ABSTRACT RAS proteins have long been considered difficult therapeutic targets, but allele‐selective inhibitors established the clinical tractability of mutant RAS. Daraxonrasib (RMC‐6236), an oral pan‐RAS inhibitor, has now extended this concept by targeting multiple mutant and wild‐type RAS proteins.
Ryo Honda
wiley   +1 more source

TRIM59 Drives Bladder Cancer Progression Through E3 Ligase‐Dependent K48‐Linked Degradation of PTRF

Cancer Science, EarlyView.
Schematic model of TRIM59‐driven BLCA progression through K48‐linked ubiquitination and proteasomal degradation of PTRF, leading to AKT activation and c‐Myc upregulation. ABSTRACT Tripartite motif‐containing 59 (TRIM59) is an E3 ubiquitin ligase implicated in multiple malignancies, but its role in bladder cancer (BLCA) remains incompletely understood ...
Junlin Gan, Xuesong Bai, Aijie Zhang, Fei Lin, Hang Tong, Tinghao Li, Ning Xu, Xinyuan Li, Zhou Yu, Hubin Yin   +9 more
wiley   +1 more source

Mdm2 targeting via PROteolysis TArgeting Chimeras (PROTAC) is efficient in p53 wildtype, p53-mutated, and abemaciclib-resistant estrogen receptor-positive cell lines and superior to mdm2 inhibition

BMC Cancer
Purpose The human double minute 2 homolog hdm2, alias mdm2, is the main negative-regulator of the tumor suppressor p53. In that capacity, mdm2 is a promising but not yet utilized molecular target for the treatment of breast cancer, however, its ...
Alina Goerg, Gerhard Piendl, Veruschka Albert, Olaf Ortmann, Anja Kathrin Wege, Gero Brockhoff   +5 more
doaj   +1 more source