Covalent allosteric inhibitors of Akt generated using a click fragment approach.
Sign Up to like & getrecommendations! Published in 2022 at "ChemMedChem"
DOI: 10.1002/cmdc.202100776
Abstract: Akt is a protein kinase that has been implicated in the progression of cancerous tumors. A number of covalent allosteric Akt inhibitors are known, and based on these scaffolds, a small library of novel potential… read more here.
Keywords: covalent; allosteric inhibitors; covalent allosteric; inhibitors akt ... See more keywords
Allosteric inhibitors of the STAT3 signaling pathway.
Sign Up to like & getrecommendations! Published in 2020 at "European journal of medicinal chemistry"
DOI: 10.1016/j.ejmech.2020.112122
Abstract: Over-expression and/or hyperactivation of signal transducer and activator of transcription 3 (STAT3) signaling are found in various human diseases, including cancer, autoimmune disorders, and inflammatory diseases. Therefore, STAT3 represents a highly promising therapeutic target for… read more here.
Keywords: inhibitors stat3; allosteric inhibitors; chemistry; signaling pathway ... See more keywords
A High-Throughput Assay to Identify Allosteric Inhibitors of the PLC-γ Isozymes Operating at Membranes.
Sign Up to like & getrecommendations! Published in 2020 at "Biochemistry"
DOI: 10.1021/acs.biochem.0c00511
Abstract: The two phospholipase C-γ (PLC-γ) isozymes are major signaling hubs and emerging therapeutic targets for various diseases, yet there are no selective inhibitors for these enzymes. We have developed a high-throughput, liposome-based assay that features… read more here.
Keywords: assay identify; plc isozymes; allosteric inhibitors; throughput assay ... See more keywords
The Dawn of Allosteric BCR-ABL1 Drugs: From a Phenotypic Screening Hit to an Approved Drug.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.2c00373
Abstract: Chronic myeloid leukemia (CML) is driven by the constitutive activity of the BCR-ABL1 fusion oncoprotein. Despite the great success of drugs that target the BCR-ABL1 ATP-binding site in transforming CML into a manageable disease, emerging… read more here.
Keywords: dawn allosteric; allosteric bcr; bcr abl1; allosteric inhibitors ... See more keywords
Covalent-Allosteric Inhibitors: Do We Get the Best of Both Worlds?
Sign Up to like & getrecommendations! Published in 2025 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.4c02760
Abstract: Covalent-allosteric inhibitors (CAIs) may achieve the best of both worlds: increased potency, long-lasting effects, and reduced drug resistance typical of covalent ligands, along with enhanced specificity and decreased toxicity inherent in allosteric modulators. Therefore, CAIs… read more here.
Keywords: allosteric inhibitors; covalent allosteric; best worlds; inhibitors get ... See more keywords
Identification of Novel Cyclobutane-Based Derivatives as Potent Acetyl-CoA Carboxylase Allosteric Inhibitors for Nonalcoholic Steatohepatitis Drug Discovery.
Sign Up to like & getrecommendations! Published in 2025 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.5c00259
Abstract: Nonalcoholic steatohepatitis (NASH) has become a leading cause of liver fibrosis and hepatocellular carcinoma; however, there are no efficient drugs for NASH therapy. Acetyl-CoA carboxylase (ACC) is a crucial enzyme regulating lipid metabolism that is… read more here.
Keywords: cyclobutane based; coa carboxylase; allosteric inhibitors; nonalcoholic steatohepatitis ... See more keywords
Discovery of Potent and Selective Allosteric Inhibitors of Protein Arginine Methyltransferase 3 (PRMT3)
Sign Up to like & getrecommendations! Published in 2018 at "Journal of Medicinal Chemistry"
DOI: 10.1021/acs.jmedchem.7b01674
Abstract: PRMT3 catalyzes the asymmetric dimethylation of arginine residues of various proteins. It is crucial for maturation of ribosomes and has been implicated in several diseases. We recently disclosed a highly potent, selective, and cell-active allosteric… read more here.
Keywords: potent selective; discovery potent; allosteric inhibitors; selective allosteric ... See more keywords
Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders.
Sign Up to like & getrecommendations! Published in 2019 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.9b00193
Abstract: Novel pyridine- and pyrimidine-based allosteric inhibitors are reported that achieve PDE4D subtype selectivity through recognition of a single amino acid difference on a key regulatory domain, known as UCR2, that opens and closes over the… read more here.
Keywords: design synthesis; fragile syndrome; allosteric inhibitors; pde4d ... See more keywords
Development and Characterization of a Fluorescent Probe for GLS1 and the Application for High-Throughput Screening of Allosteric Inhibitors.
Sign Up to like & getrecommendations! Published in 2019 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.9b01035
Abstract: Glutaminase (GLS1) is a cancer energy metabolism protein which plays a predominant role in cell growth and proliferation. Due to its major involvement in malignant tumor, small-molecule GLS1 inhibitors are urgently needed to assess its… read more here.
Keywords: allosteric inhibitors; development characterization; chemistry; fluorescent ... See more keywords
Chirality-Driven Mode of Binding of α-Aminophosphonic Acid-Based Allosteric Inhibitors of the Human Farnesyl Pyrophosphate Synthase (hFPPS).
Sign Up to like & getrecommendations! Published in 2019 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.9b01104
Abstract: Thienopyrimidine-based allosteric inhibitors of the human farnesyl pyrophosphate synthase (hFPPS), characterized by a chiral α-aminophosphonic acid moiety, were synthesized as enantiomerically enriched pairs and their binding mode was investigated by X-ray crystallography. A general consensus… read more here.
Keywords: farnesyl pyrophosphate; based allosteric; human farnesyl; allosteric inhibitors ... See more keywords
Mechanism of Allosteric Inhibition of the Enzyme IspD by Three Different Classes of Ligands.
Sign Up to like & getrecommendations! Published in 2017 at "ACS chemical biology"
DOI: 10.1021/acschembio.7b00004
Abstract: Enzymes of the nonmevalonate pathway of isoprenoid biosynthesis are attractive targets for the development of herbicides and drugs against infectious diseases. While this pathway is essential for many pathogens and plants, mammals do not depend… read more here.
Keywords: different classes; mechanism; allosteric inhibitors; inhibition ... See more keywords