Dynamic extracellular vestibule of human SERT: unveiling druggable potential with novel high-affinity allosteric inhibitors [PDF]
, 2023 The serotonin transporter (SERT) tightly regulates synaptic serotonin levels and has been the primary target of antidepressants. Binding of inhibitors to the allosteric site of human SERT (hSERT) impedes the dissociation of antidepressants bound at the ...
Benny, Bang-Andersen +6 more
core +1 more source
Small-molecule allosteric inhibitors of BAX [PDF]
Nature Chemical Biology, 2019 BAX is a critical effector of the mitochondrial cell death pathway in response to a diverse range of stimuli in physiological and disease contexts. Upon binding by BH3-only proteins, cytosolic BAX undergoes conformational activation and translocation, resulting in mitochondrial outer-membrane permeabilization.
Thomas P. Garner +5 more
openaire +2 more sources
Macrocyclic Peptides as Allosteric Inhibitors of Nicotinamide N-Methyltransferase (NNMT) [PDF]
, 2020 Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide to form 1-methylnicotinamide using S-adenosyl-l-methionine (SAM) as the methyl donor. The complexity of the role of NNMT in healthy and disease states is slowly being elucidated and provides
Nathaniel, Martin +7 more
core +2 more sources
The discovery of high affinity and metabolically stable allosteric cyclin-dependent kinase 2 (CDK2) inhibitors from screening through lead optimization [PDF]
, 2022 Despite the status of cyclin-dependent kinase 2 (CDK2) as a validated target for both anticancer and contraceptive indications, a CDK2 inhibitor with exquisite selectivity has been historically challenging, largely due to the structural similarity of the
Kristen, John +16 more
core +2 more sources
Allo-network drugs: Extension of the allosteric drug concept to protein-protein interaction and signaling networks [PDF]
, 2013 Allosteric drugs are usually more specific and have fewer side effects than orthosteric drugs targeting the same protein. Here, we overview the current knowledge on allosteric signal transmission from the network point of view, and show that most ...
Csermely, Péter +3 more
core +2 more sources
Computational Study of SARS-CoV-2 RNA Dependent RNA Polymerase Allosteric Site Inhibition
Molecules, 2021 The COVID-19 pandemic has caused millions of fatalities since 2019. Despite the availability of vaccines for this disease, new strains are causing rapid ailment and are a continuous threat to vaccine efficacy.
Shah Faisal +6 more
doaj +1 more source
The origin of potency and mutant-selective inhibition by bivalent ATP-allosteric EGFR inhibitors [PDF]
, 2023 Targeted small-molecule therapies in mutant epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) have undergone several generations of development in response to acquired drug resistance.
David A, Scott +17 more
core +2 more sources
Molecules, 2020 Casein kinase II (CK2) is considered as an attractive cancer therapeutic target, and recent efforts have been made to develop its ATP-competitive inhibitors.
Chunqiong Li +6 more
doaj +1 more source
Discovery of Potential GSK-3β Allosteric Modulators for Alzheimer’s Disease [PDF]
, 2023 Glycogen Synthase Kinase-3 beta (GSK-3β) is a validated target-enzyme associated with Alzheimer’s Disease (AD). Usage of allosteric inhibitors of this enzyme represents a valid and promising therapeutic strategy due to their selective and subtle ...
Alexander, Tropsha +6 more
core +2 more sources
Allosteric inhibition enhances the efficacy of ABL kinase inhibitors to target unmutated BCR-ABL and BCR-ABL-T315I [PDF]
, 2012 Background: Chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphatic leukemia (Ph + ALL) are caused by the t(9;22), which fuses BCR to ABL resulting in deregulated ABL-tyrosine kinase activity.
Ruimi, Nili +18 more
core +2 more sources