Modeling Epac1 interactions with the allosteric inhibitor AM-001 by co-solvent molecular dynamics
Sign Up to like & getrecommendations! Published in 2020 at "Journal of Computer-Aided Molecular Design"
DOI: 10.1007/s10822-020-00332-y
Abstract: The exchange proteins activated by cAMP (EPAC) are implicated in a large variety of physiological processes and they are considered as promising targets for a wide range of therapeutic applications. Several recent reports provided evidence… read more here.
Keywords: allosteric inhibitor; modeling epac1; molecular dynamics; interactions allosteric ... See more keywords
Discovery of a First-In-Class Covalent Allosteric Inhibitor of SUMO E1 Activating Enzyme.
Sign Up to like & getrecommendations! Published in 2019 at "Cell chemical biology"
DOI: 10.1016/j.chembiol.2019.02.006
Abstract: SUMOylation is a post-translational modification with important roles in normal physiology and whose dysregulation is associated with human diseases. In this issue of Cell Chemical Biology, Li et al. (2019) describe a covalent, allosteric inhibitor of… read more here.
Keywords: covalent allosteric; allosteric inhibitor; biology; inhibitor sumo ... See more keywords
An allosteric inhibitor of bacterial Hsp70 chaperone potentiates antibiotics and mitigates resistance.
Sign Up to like & getrecommendations! Published in 2021 at "Cell chemical biology"
DOI: 10.1016/j.chembiol.2021.11.004
Abstract: DnaK is the bacterial homolog of Hsp70, an ATP-dependent chaperone that helps cofactor proteins to catalyze nascent protein folding and salvage misfolded proteins. In the pathogen Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), DnaK… read more here.
Keywords: bacterial hsp70; allosteric inhibitor; inhibitor bacterial; chaperone ... See more keywords
Identification of natural allosteric inhibitor for Akt1 protein through computational approaches and in vitro evaluation.
Sign Up to like & getrecommendations! Published in 2017 at "International journal of biological macromolecules"
DOI: 10.1016/j.ijbiomac.2016.12.025
Abstract: Akt, a serine/threonine protein kinase, is often hyper activated in breast and prostate cancers, but with poor prognosis. Allosteric inhibitors regulate aberrant kinase activity by stabilizing the protein in inactive conformation. Several natural compounds have… read more here.
Keywords: allosteric inhibitor; inactive conformation; natural allosteric; inhibitor akt1 ... See more keywords
Memory enhancing effects of BPN14770, an allosteric inhibitor of phosphodiesterase-4D, in wild-type and humanized mice
Sign Up to like & getrecommendations! Published in 2018 at "Neuropsychopharmacology"
DOI: 10.1038/s41386-018-0178-6
Abstract: Inhibitors of phosphodiesterase-4 (PDE4) have beneficial effects on memory in preclinical and clinical studies. Development of these drugs has stalled due to dose-limiting side effects of nausea and emesis. While use of subtype-selective inhibitors (i.e.,… read more here.
Keywords: effects bpn14770; allosteric inhibitor; bpn14770 allosteric; wild type ... See more keywords
HKB99, an allosteric inhibitor of phosphoglycerate mutase 1, suppresses invasive pseudopodia formation and upregulates plasminogen activator inhibitor-2 in erlotinib-resistant non-small cell lung cancer cells
Sign Up to like & getrecommendations! Published in 2020 at "Acta Pharmacologica Sinica"
DOI: 10.1038/s41401-020-0399-1
Abstract: Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as erlotinib, remains a major challenge in the targeted therapy of non-small cell lung cancer (NSCLC). HKB99 is a novel allosteric inhibitor of… read more here.
Keywords: allosteric inhibitor; inhibitor; erlotinib resistant; invasive pseudopodia ... See more keywords
Molecular mechanism of a covalent allosteric inhibitor of SUMO E1 activating enzyme
Sign Up to like & getrecommendations! Published in 2018 at "Nature Communications"
DOI: 10.1038/s41467-018-07015-1
Abstract: E1 enzymes activate ubiquitin (Ub) and ubiquitin-like modifiers (Ubls) in the first step of Ub/Ubl conjugation cascades and represent potential targets for therapeutic intervention in cancer and other life-threatening diseases. Here, we report the crystal… read more here.
Keywords: covalent allosteric; allosteric inhibitor; mechanism; sumo ... See more keywords
Allosteric inhibitor of β-catenin selectively targets oncogenic Wnt signaling in colon cancer
Sign Up to like & getrecommendations! Published in 2020 at "Scientific Reports"
DOI: 10.1038/s41598-020-60784-y
Abstract: Abnormal regulation of β-catenin initiates an oncogenic program that serves as a main driver of many cancers. Albeit challenging, β-catenin is an attractive drug target due to its role in maintenance of cancer stem cells… read more here.
Keywords: allosteric inhibitor; inhibitor catenin; catenin; cancer ... See more keywords
Structure-activity exploration of a small-molecule allosteric inhibitor of T790M/L858R double mutant EGFR
Sign Up to like & getrecommendations! Published in 2022 at "Journal of Enzyme Inhibition and Medicinal Chemistry"
DOI: 10.1080/14756366.2022.2145284
Abstract: Abstract EGFR is a protein kinase whose aberrant activity is frequently involved in the development of non-small lung cancer (NSCLC) drug resistant forms. The allosteric inhibition of this enzyme is currently one among the most… read more here.
Keywords: structure activity; allosteric inhibitor; mutant egfr; egfr ... See more keywords
Discovery of the SHP2 allosteric inhibitor 2-((3R,4R)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-5-(2,3-dichlorophenyl)-3-methylpyrrolo[2,1-f][1,2,4] triazin-4(3H)-one
Sign Up to like & getrecommendations! Published in 2022 at "Journal of Enzyme Inhibition and Medicinal Chemistry"
DOI: 10.1080/14756366.2022.2151594
Abstract: Abstract The non-receptor protein tyrosine phosphatase (PTP) SHP2 encoded by the PTPN11 gene is a critical regulator in a number of cellular signalling processes and pathways, including the MAPK and the immune-inhibitory programmed cell death… read more here.
Keywords: amino methyl; shp2; allosteric inhibitor; shp2 allosteric ... See more keywords