Results 91 to 100 of about 692,160 (279)

TOLLIP Inhibits Psoriasis Progression via Suppressing PKM2‐Mediated Glycolysis in Keratinocytes

Advanced Science, EarlyView.
In this study, we identify TOLLIP as a critical regulator of psoriasis pathogenesis through its modulation of glycolytic metabolism. Our findings establish the TOLLIP‐PKM2‐glycolysis axis as a key mechanism linking metabolic reprogramming to psoriasis pathogenesis, and propose TOLLIP as a promising therapeutic target.
Xiuhuan Jiang, Guoying Miao, Na Shen, Qingxia Han, Xiaoru Han, Zichang Qiao, Kexin Feng, Zhuo Tan, Yaguang Wang, Xiuhua Liu, Chen Wu, Zhenzhen Yan   +11 more
wiley   +1 more source

Somatic Evolution of a Germline Antibody Expands its Breadth to Neutralize Early SARS‐CoV‐2 Omicron Variants

Advanced Science, EarlyView.
Engineering of the 148‐germline (148‐GL) antibody reveals a roadmap for overcoming SARS‐CoV‐2 viral escape. By introducing four specific somatic hypermutations, the resulting 148‐M4 variant restores potent neutralization against Omicron BA.1 and BA.4/5.
Huibin Lv, Ziqi Feng, Qi Wen Teo, Chunke Chen, Akshita B. Gopal, Danbi Choi, Timothy J. C. Tan, Yun Sang Tang, Lewis Siu, Armita Nourmohammad, Roberto Bruzzone, Ian A. Wilson, Meng Yuan, Nicholas C. Wu, Chris K. P. Mok   +14 more
wiley   +1 more source

Druggable cavities and allosteric modulators of the cell division cycle 7 (CDC7) kinase

Journal of Enzyme Inhibition and Medicinal Chemistry
Cell division cycle 7 kinase (CDC7) has been found overexpressed in many cancer cell lines being also one of the kinases involved in the nuclear protein TDP-43 phosphorylation in vivo.
Elisa Rojas-Prats, Loreto Martinez-Gonzalez, Carmen Gil, David Ramírez, Ana Martinez   +4 more
doaj   +1 more source

Allosteric AKT inhibitors as a targeted cancer therapy [PDF]

Cancer Biology & Therapy, 2010
Commentary to:An allosteric Akt inhibitor effectively blocks Akt signaling and tumor growth with only transient effects on glucose and insulin levels in vivoCraig Cherrin, Kathleen Haskell, Bonnie Howell, Raymond Jones, Karen Leander, Ronald Robinson, Aubrey Watkins, Mark Bilodeau, Jacob Hoffman, Philip Sanderson, George Hartman, Elizabeth Mahan ...
openaire   +2 more sources

Systematic Position Mapping of Split CRISPR‐Cas12a Activators Enables Highly Sensitive miRNA Detection and Cancer Cell Stratification

Advanced Science, EarlyView.
ABSTRACT Amplification‐free Cas12a diagnostics with split crRNA enable rapid and programmable target recognition, yet insufficient understanding of DNA activator architecture prevents predictable control over trans‐cleavage activity and sensitivity. Here we systematically map over 200 split DNA activator configurations by introducing nicks at every ...
Xiaoyan Tang, Zhe Li, Yuning Lu, Miao Ma, Zijian Mo, Jiajun Ke, Xinyu Luan, Tiangang Luan, Junqiu Zhai   +8 more
wiley   +1 more source

Cancer‐Associated BCL‐2 Mutants Reveal Mechanisms Towards Venetoclax Resistance

Advanced Science, EarlyView.
Venetoclax (VEN) resistance in chronic lymphocytic leukemia arises from diverse BCL2 mutations. We map mechanisms contributing to VEN resistance across common BCL‐2 variants. G101V and D103Y reduce drug binding and increase sequestration of pro‐apoptotic proteins. V156D blocks VEN allosterically.
Jonas Aufdermauer, Ian de Ridder, Mahjoobeh Ehsani, Marasim Khan, Justin Kale, Lukas P. Frenzel, David Andrews, Spyridoula Karamanou, Ana J. Garcia‐Saez, Geert Bultynck   +9 more
wiley   +1 more source

Pyrazole‐Derived Antibacterial Compounds Effectively Treat Methicillin‐Resistant Staphylococcus Aureus Infections by Inhibiting Aspartate Transcarbamoylase

Advanced Science, EarlyView.
This study unveils a novel antibacterial mechanism against MRSA, in which the compound Py‐27 selectively targets and inhibits aspartate transcarbamoylase (ATCase), a key enzyme in pyrimidine synthesis. This inhibition disrupts DNA replication, induces oxidative damage, leading to potent bactericidal activity.
Xiaorong Yang, Xinyuan Cao, Lixia Dai, Feng Yang, Jing Wang, Yudong Ma, Tong Bu, Zile Gong, Xueyan Liu, Changcai Bai, Xiaolou Miao, Xiaofei Shang   +11 more
wiley   +1 more source

Unveiling Allosteric Regulation and Binding Mechanism of BRD9 through Molecular Dynamics Simulations and Markov Modeling

Molecules
Bromodomain-containing protein 9 (BRD9) is a key player in chromatin remodeling and gene expression regulation, and it is closely associated with the development of various diseases, including cancers.
Bin Wang, Jian Wang, Wanchun Yang, Lu Zhao, Benzheng Wei, Jianzhong Chen   +5 more
doaj   +1 more source

The Natural Product Corramycin Acts as a DNA Gyrase Poison and Overcomes Fluoroquinolone Resistance in Mycobacterium tuberculosis

Advanced Science, EarlyView.
Corramycin, a myxobacterial natural product antibiotic, exhibits potent bactericidal activity against multidrug‐resistant Mycobacterium tuberculosis. The compound hijacks bacterial transporters such as BacA and OppABCD to enter the cell and inhibits DNA synthesis through a previously unrecognized mode of DNA gyrase poisoning, locking the enzyme in an ...
Franziska Fries, Jennifer Herrmann, Michael Dal Molin, Yaëlle Wormser, Timo Risch, Yunsheng Gao, Gareth Prosser, Francesca Gubellini, Ariel Mechaly, Joshua B. Wallach, Anthony Castro, Arka Banerjee, Sari Rasheed, Alexander Horn, Mathias Müsken, Michael Kurz, Lindsay Sonnenkalb, Viola Dreyer, Stefan Niemann, Sönke Andres, Dirk Schnappinger, Uli Kazmaier, Norbert Reiling, Rolf Müller, Jan Rybniker, Stéphanie Petrella   +25 more
wiley   +1 more source

Molecular Dynamics-Assisted Discovery of Novel Phosphodiesterase-5 Inhibitors Targeting a Unique Allosteric Pocket

Molecules
Phosphodiesterase-5 (PDE5) is a potent therapeutic target for the treatment of male erectile dysfunction and pulmonary arterial hypertension with several drugs available on the market.
Weihao Luo, Runduo Liu, Xinlin Cai, Qian Zhou, Chen Zhang   +4 more
doaj   +1 more source