Results 71 to 80 of about 692,160 (279)

The Development of Allosteric Inhibitors of IKK2 [PDF]

, 2020
IκB kinase 2 (IKK2) is the essential kinase in the activation pathway of NF-κB and it is a critical regulator of inflammation which is inducibly activated by a host of stimuli.
Hotchkiss, Sonjiala Jackson
core   +1 more source

In Silico Discovery of a Novel Potential Allosteric PI3Kα Inhibitor Incorporating 3-(2-Chloro-5-fluorophenyl)isoindolin-1-one to Target Head and Neck Squamous Cell Carcinoma

Biology
Phosphatidylinositol 3-kinase alpha (PI3Kα) is frequently mutated in head and neck squamous cell carcinoma (HNSCC), leading to the constitutive activation of the PI3K/Akt pathway, which promotes tumor cell proliferation, survival, and metastasis.
Wenqing Jia, Xianchao Cheng
doaj   +1 more source

Allosteric IGF-1R Inhibitors

, 2016
Targeting allosteric protein sites is a promising approach to interfere selectively with cellular signaling cascades. We have discovered a novel class of allosteric insulin-like growth factor-I receptor (IGF-1R) inhibitors. 3-Cyano-1H-indole-7-carboxylic
Timo Heinrich (1992388), Henning Böttcher (2276560), Andree Blaukat (2276557), Ulrich Grädler (1992397), Adam Shutes (2276554)   +4 more
core   +1 more source

Synergy and Antagonism between Allosteric and Active‐Site Inhibitors of Abl Tyrosine Kinase

, 2021
Allosteric inhibitors of Abl kinase are being explored in the clinic, often in combination with ATP‐site inhibitors of Abl kinase. However, there are conflicting data on whether both ATP‐competitive inhibitors and myristoyl‐site allosteric inhibitors can
Bochar, Daniel A., Daniel A. Bochar, Taylor K. Johnson, Nathalie M. Vandecan, Vandecan, Nathalie M., Matthew B. Soellner, Johnson, Taylor K., Jessica Furtado, Phadke, Sameer, Soellner, Matthew B., Michael P. Agius, Furtado, Jessica, Sameer Phadke, Agius, Michael P.   +13 more
core   +1 more source

In vitro and in silico modelling of ROS1‐positive non‐small cell lung cancer reveals fusion‐dependent tyrosine kinase inhibitor responses

Molecular Oncology, EarlyView.
Drug resistance limits treatment success in a subset of lung cancers driven by ROS1 gene alterations. Using patient‐derived cells and computer simulations, we studied three key mutations and how they affect five targeted drugs. The mutations reduced drug effectiveness in different ways by altering protein structure and behavior.
Farhan Ul Haq, Marc Terrones, Felicia Rodrigues Fortes, Anne Schepers, Alessia Denis, Christophe Deben, Ken Op de Beeck, Guy Van Camp, Geert Vandeweyer   +8 more
wiley   +1 more source

Protein Phosphatases: A Neglected Target Family for Drug Discovery

CHIMIA, 2022
The gene family of protein phosphatases is a rich but under-exploited source of therapeutically validated drug targets modulating signal transduction pathways.
Joe Lewis, Gerhard Müller
doaj   +1 more source

Translating whole‐genome doubling into precision medicine in cancer

Molecular Oncology, EarlyView.
Whole‐genome doubling creates a WGD‐positive tumor state characterized by persistent chromosomal instability, karyotypic diversification, and cellular stress. These same biological pressures drive aggressive tumor evolution while exposing therapeutic vulnerabilities, providing a rationale for WGD‐informed precision medicine. Whole‐genome doubling (WGD)
Sejung Lee, Junghyeok Lim, Jinhyuk Bhin
wiley   +1 more source

Computational Insights into Natural Antischistosomal Metabolites as SmHDAC8 Inhibitors: Molecular Docking, ADMET Profiling, and Molecular Dynamics Simulation

Metabolites, 2023
Schistosomiasis is a neglected tropical disease with a significant socioeconomic impact. It is caused by several species of blood trematodes from the genus Schistosoma, with S. mansoni being the most prevalent.
Abdulrahim A. Alzain, Rua M. Mukhtar, Nihal Abdelmoniem, Fatima A. Elbadwi, Amira Hussien, Elrashied A. E. Garelnabi, Wadah Osman, Asmaa E. Sherif, Amgad I. M. Khedr, Kholoud F. Ghazawi, Waad A. Samman, Sabrin R. M. Ibrahim, Gamal A. Mohamed, Ahmed Ashour   +13 more
doaj   +1 more source

Structural Dynamics and Allosteric Signaling in Ionotropic Glutamate Receptors [PDF]

, 2013
Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate excitatory neurotransmission events in the central nervous system. All distinct classes of iGluRs (AMPA, NMDA, Kainate) are composed of an N-terminal domain (NTD) and a ...
Dutta, Anindita
core  

NAPRT loss promotes lung tumor initiation and growth through AKT signaling independently of NAD+ biosynthesis

Molecular Oncology, EarlyView.
Loss of NAPRT promotes lung tumor initiation and growth through a noncanonical mechanism, independent of its role in NAD+ biosynthesis. Mechanistically, NAPRT depletion activates the mTORC2‐driven AKT/β‐catenin signaling axis to enhance clonogenic and invasive phenotypes. Furthermore, lung‐specific Naprt deletion significantly increases tumor burden in
Myung Joon Oh, Ji Yun Jang, Yoon Jeon, Gi‐Cheon Kim, Hwanho Lee, Jooyoung Lee, Ju‐Hwa Kim, Hakhyun Kim, Minjee Kim, Ho‐Keun Kwon, Ho Lee, Hyun Seok Kim   +11 more
wiley   +1 more source