Results 121 to 130 of about 2,925,762 (288)

A Novel Pak1 Activator Ameliorates ER Stress for HFpEF Therapy

Advanced Science, EarlyView.
Chronic metabolic stress is a major contributor to HFpEF progression. Under prolonged metabolic stress, Pak1 activity becomes impaired, contributing to disrupted ER proteostasis, cardiomyocyte apoptosis, fibrosis, and diastolic dysfunction. Mechanistically, Pak1 overexpression activates the ERK1/2–MNK1–eIF4E signaling axis, promotes translational ...
Honglin Xu, Hongyuan Zhang, Tayyiba Azam, Susanne S. Hille, Yingjuan Liu, Min Zi, Jiaqing Lang, He Yu, Yujia Cao, Bernard D. Keavney, Tamer M. A. Mohamed, Jessica M. Miller, Riham R. E. Abouleisa, Ming Xu, Elizabeth J. Cartwright, Oliver J. Müller, Ming Lei, Xin Wang   +17 more
wiley   +1 more source

Chemical, target, and bioactive properties of allosteric modulation.

PLoS Computational Biology, 2014
Allosteric modulators are ligands for proteins that exert their effects via a different binding site than the natural (orthosteric) ligand site and hence form a conceptually distinct class of ligands for a target of interest.
Gerard J P van Westen, Anna Gaulton, John P Overington   +2 more
doaj   +1 more source

Novel Allosteric Sites on Ras for Lead Generation

PLoS ONE, 2011
Aberrant Ras activity is a hallmark of diverse cancers and developmental diseases. Unfortunately, conventional efforts to develop effective small molecule Ras inhibitors have met with limited success. We have developed a novel multi-level computational approach to discover potential inhibitors of previously uncharacterized allosteric sites.
Grant, Barry J, Lukman, Suryani, Hocker, Harrison J, Sayyah, Jaqueline, Brown, Joan Heller, McCammon, J Andrew, Gorfe, Alemayehu A   +6 more
openaire   +6 more sources

DDX3x Regulates NINJ1 Transcription via Histone Lactylation in Sepsis Associated‐Acute Kidney Injury

Advanced Science, EarlyView.
This study identifies a potential therapeutic approach for sepsis‐associated acute kidney injury (SA‐AKI). We found that during SA‐AKI, reduced expression of DDX3x in renal tubular epithelial cells mediates histone delactylation, which in turn upregulates NINJ1 transcription and triggers tubular cell death. Conversely, Odetiglucan confers protection by
Hongyu Liang, Jihong Jiang, Huanxin Yin, Chunyan Liu, Hongjun Huang, Yan Luo, Minmin Zhu, Qiuyun Wang   +7 more
wiley   +1 more source

A potential allosteric inhibitor of SARS-CoV-2 main protease (Mpro) identified through metastable state analysis

Frontiers in Molecular Biosciences
Anti-COVID19 drugs, such as nirmatrelvir, have been developed targeting the SARS-CoV-2 main protease, Mpro, based on the critical requirement of its proteolytic processing of the viral polyproteins into functional proteins essential for viral replication.
Asma Fatima, Anupriya M. Geethakumari, Wesam S. Ahmed, Kabir H. Biswas   +3 more
doaj   +1 more source

Transcription Factor HOXC11 Drives Colorectal Cancer Progression and Metastasis via CAMK2A‐Dependent CXCL5 Upregulation

Advanced Science, EarlyView.
HOXC11 drives colorectal cancer progression by transcriptionally activating CAMK2A, which triggers NF‐κB–dependent CXCL5 upregulation. CXCL5–CXCR2 signaling further reinforces HOXC11 expression through the ERK1/2–SP1 axis, forming a prometastatic positive feedback loop that is effectively disrupted by combined CAMK2A and CXCR2 inhibition.
Qingyang Sun, Hengjie Xu, Sheng Yang, Jiahui Zhou, Chuanxin Tian, Hongxu Nie, Chi Jin, Tuo Wang, Zhihao Chen, Junwei Tang, Yifei Feng, Xiaowei Wang, Yueming Sun   +12 more
wiley   +1 more source

A Site‐Aware Representation Learning Framework For Unified Molecular Interaction Modeling and Generative Design

Advanced Science, EarlyView.
MolDBG is a site‐aware, sequence‐only framework that unifies drug‐target affinity prediction, binding‐site identification, and affinity‐conditioned molecular generation for structured proteins. Guided by multi‐task binding‐site supervision, it aligns interaction‐critical residues before learning drug‐target representations and simultaneously infers ...
Gang Luo, Qianqian Zhang, Chenhao Wang, Zhiheng Yi, Alex Jinpeng Wang, Jing Tang, Min Li   +6 more
wiley   +1 more source

Selective Modulation of OTUB1 Noncanonical Function via a bioPhosTAC Strategy

Advanced Science, EarlyView.
This work positions the versatile performance of the peptide‐based bioPhosTAC platform for dissecting phosphorylation‐dependent biology and expanding the scope of induced‐proximity technologies. We demonstrated that selective manipulation of a tyrosine phosphorylation site is sufficient to propagate coordinated cellular consequences.
Seung Un Seo, Seon Min Woo, Minhyeong Choi, Soeun Rhee, Simmyung Yook, Donghyuk Shin, Kwang‐Su Park, Taeg Kyu Kwon   +7 more
wiley   +1 more source

Two allosteric modulators binding to the same site.

, 2019
Allosteric interaction between tracer X and allosteric modulators A and B at receptor R, assuming that the two allosteric modulators compete for the same allosteric site.
Esam E. El-Fakahany (339452), Alena Randáková (339451), Jan Jakubík (339449), Vladimír Doležal (339453)   +3 more
core   +1 more source

Entropy‐Driven Physical Amplification in Multivalent Biosensing

Advanced Science, EarlyView.
Detecting scarce molecules usually demands enzymatic amplification such as PCR. A statistical‐mechanical theory now reveals a purely physical alternative: distributing a fixed binding strength over more linker arms exponentially lowers the concentration at which multivalent sensors switch on.
Yuhan Peng, Xiuyang Xia, Ran Ni
wiley   +1 more source