Results 121 to 130 of about 107,657 (326)

Molecular Glue cc‐885 Inhibits VHL‐Deficient Clear Cell Renal Cell Carcinoma via ETS1 Degradation

Advanced Science, EarlyView.
VHL‐deficient kidney cancer lacks effective treatments. This study reveals that the molecular glue degrader cc‐885 hijacks the cellular recycling system to selectively destroy the oncogenic protein ETS1, effectively killing VHL‐mutant tumors. Combining CC‐885 with the approved drug belzutifan achieves powerful synergy, offering a promising new ...
Taowei Yang, Qihao Li, Kun Ye, Kezhi Liu, Mi Zhou, Minyu Chen, Lican Liao, Kangbo Huang, Zhu Wang, Qiong Deng, Jieyan Wang, Meiyu Jin, Xu Chen, Hui Liang, Jiaxing Zhang, Junhang Luo   +15 more
wiley   +1 more source

The positive allosteric GABAB receptor modulator rac-BHFF enhances baclofen-mediated analgesia in neuropathic mice.

, 2016
Neuropathic pain is associated with impaired inhibitory control of spinal dorsal horn neurons, which are involved in processing pain signals. The metabotropic GABAB receptor is an important component of the inhibitory system and is highly expressed in ...
Malherbe, Pari, Benke, Dietmar, Khaled Zemoura, William T. Ralvenius, Zemoura, Khaled, Ralvenius, William T, Pari Malherbe, Dietmar Benke   +7 more
core   +1 more source

Dose‐Dependent Reprogramming of Chromatin Accessibility by SOX4 Drives the Transcriptional Response to Iron Overload

Advanced Science, EarlyView.
This study demonstrates that iron overload triggers widespread chromatin compaction and transcriptional repression in human granulosa cells, recapitulating features of endometriosis. The epigenetic reprogramming is orchestrated by a TFEB‐SOX4‐SWI/SNF axis, with SOX4 acting as a central, dosage‐sensitive regulator.
Feifei Li, Yaoqiu Wu, Guangyu Yang, Jingyi Lai, Xiaoyue Sun, Liyan Wang, Xiaoli Li, Jing Zhang, Qingxue Zhang, Hui Chen, Haiyan Lin, Bingxiang Xu, Junfeng Zhang, Hailong Wang, Anming Meng, Chunwei Cao   +15 more
wiley   +1 more source

Targeting Supramolecular Active Complexes of Nav1.7/Nav1.8 to Relieve Chronic Neuropathic Pain

Advanced Science, EarlyView.
In mice and patients with severe chronic neuropathic pain (NP), Nav1.7, Nav1.8, TrkB, and five cytoskeletal proteins form supramolecular active complexes (SMACs) with polygonal lattice structures as noxious signal amplifiers in dorsal root ganglion (DRG) neurons.
Liting Sun, Hang Xian, Yunxin Shi, Taotan Yang, Hongyan Shuai, Wenchao Hu, Siying Fei, Miao Xu, Taoyuan Yang, Ruilong Xia, Ting Wen, Fengting Zhu, Yan Fu, Yang Li, Wei Xia, Ran Qian, Yuanying Liu, Zhicheng Tian, Lamei Li, Qian Zhou, Lize Xiong, Rui Cong, Ceng Luo, Shengxi Wu, Xiafeng Shen, Xin Yu, Rou‐Gang Xie, Changgeng Peng   +27 more
wiley   +1 more source

Divergent Roles of mGlu2 and mGlu3 Receptors in Amyloid‐β Production and Cognitive Dysfunctions in Alzheimer's Disease

Advanced Science, EarlyView.
This study explores the opposing effects of the mGluR2 and mGluR3 receptors on amyloid precursor protein processing. mGluR2 promotes amyloidogenic cleavage, while mGluR3 favors non‐amyloidogenic pathways. Using a brain‐penetrant nanobody as a mGluR2 positive allosteric modulator, the study uncovers how its chronic activation aggravates amyloid‐β burden
Pierre‐André Lafon, Mireille Elodie Tsitokana, Ugo Guy Alenda, Yen‐Ling Lian, Clémentine Eva Philibert, Mathieu Oosterlaken, Marta Cimadevila, Gaëlle Dudon, Jessica Monnic, Salomé Roux, Julie Bessié, Séverine Diem, Franck Vandermoere, Laurent Prézeau, Patrick Chames, Julie Kniazeff, Sylvie Claeysen, Anaïs Menny, Jean‐Philippe Pin, Véronique Perrier, Jianfeng Liu, Philippe Rondard   +21 more
wiley   +1 more source

The AMPA receptor positive allosteric modulator S 47445 rescues in vivo CA3‐CA1 long‐term potentiation and structural synaptic changes in old mice

Neuropharmacology, 2017
&NA; Positive allosteric modulators of &agr;‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors (AMPARs) are small molecules that decrease deactivation of AMPARs via an allosteric site.
A. Giralt, M. A. Gómez-Climent, R. Alcalá, S. Bretin, D. Bertrand, José María Delgado‐García, E. Pérez‐Navarro, J. Alberch, A. Gruart   +8 more
semanticscholar   +1 more source

Concentration dependence of the interaction of two allosteric modulators binding each to its own allosteric site.

, 2019
Upper row, simulation of tracer binding (ordinate) in the presence two allosteric modulators A and B each binding to its own site, where A is either positive (left) or negative (right) and B is negative allosteric modulator.
Esam E. El-Fakahany (339452), Alena Randáková (339451), Jan Jakubík (339449), Vladimír Doležal (339453)   +3 more
core   +1 more source

Kinsenoside Targets IDH1 to Restore Microglial Immune‐Metabolic Homeostasis for Alzheimer's Disease Therapy

Advanced Science, EarlyView.
Dysregulated TCA cycle contributes to Alzheimer's disease (AD) pathogenesis. Here, we show that microglial isocitrate dehydrogenase 1 (IDH1) is a critical driver. Elevated IDH1 disrupts citrate metabolism and mitochondrial function, exacerbating AD pathology.
Qianqian Li, Yajin Liao, Yan‐bo Zhao, Hongxing Wu, Tong Jin, Shuoshuo Li, Yuhan Liu, Peng Li, Songying Ouyang, Zekai Li, YuTing Xia, Qian Hua, Rui‐Yuan Pan, Zengqiang Yuan   +13 more
wiley   +1 more source

T‐495, a novel low cooperative M1 receptor positive allosteric modulator, improves memory deficits associated with cholinergic dysfunction and is characterized by low gastrointestinal side effect risk

Pharmacology Research & Perspectives, 2020
M1 muscarinic acetylcholine receptor (M1R) activation can be a new therapeutic approach for the treatment of cognitive deficits associated with cholinergic hypofunction. However, M1R activation causes gastrointestinal (GI) side effects in animals.
Takao Mandai, Yuu Sako, Emi Kurimoto, Yuji Shimizu, Minoru Nakamura, Makoto Fushimi, Ryouta Maeda, Maki Miyamoto, Haruhide Kimura   +8 more
doaj   +1 more source

SDS‐CRISPR for Single‐Nucleotide Variant Detection

Advanced Science, EarlyView.
Structure‐disruption‐sensitive CRISPR (SDS‐CRISPR) converts structural instability into single‐nucleotide precision, thereby overcoming mismatch tolerance in canonical Cas12a and enabling versatile diagnostics across DNA, RNA, and microRNA targets. When applied to rapid IDH1 mutation detection for glioma genotyping and integrated with lateral‐flow ...
Xin Guan, Chong Guo, Jiongyu Zhang, Rui Yang, Yerramsetti Ramachandra, Chengyu Hou, Minjie Pei, Shuo Zhang, Kurt T. Schalper, Xingye Liu, Qian Wu, Ketan R. Bulsara, Changchun Liu   +12 more
wiley   +1 more source