Results 121 to 130 of about 19,325 (262)

The Race to Salvage Glucocerebrosidase: Understanding Small‐Molecule Therapies for GBA1‐Associated Parkinsonism

Movement Disorders, EarlyView.
Variants in GBA1, the gene encoding the lysosomal enzyme glucocerebrosidase, cause Gaucher disease and confer an increased risk for parkinsonism. Strategies using small molecules can improve the function of glucocerebrosidase in lysosomes. A clear understanding of the mechanism‐of‐action of these compounds will facilitate development of GBA1‐modulating
Mark J. Henderson, Tiffany C. Chen, Logan M. Glasstetter, Yu Chen, Juan J. Marugan, Ellen Sidransky   +5 more
wiley   +1 more source

Allosteric Modulators of Drug Targets [PDF]

Journal of Medicinal Chemistry, 2018
openaire   +2 more sources

Smart Integration of Structural Biology and Medicinal Chemistry to Unlock Target‐Driven Drug Discovery

Medicinal Research Reviews, EarlyView.
ABSTRACT To enhance drug discovery efforts, medicinal chemists should evaluate, filter, and utilize relevant structural information about target proteins. Acquiring and interpreting protein structures is crucial for elucidating ligand‐receptor interactions and addressing ADME‐related considerations, making it an essential aspect of medicinal chemistry.
Matteo Rossi Sebastiano, Giulia Apprato, Serena Francisco, Giuseppe Ermondi, Giulia Caron   +4 more
wiley   +1 more source

Discovery of VU6052254: A Novel, Potent M₁ Positive Allosteric Modulator. [PDF]

ACS Chem Neurosci
Engers JL, Bungard JD, Presley CC, Zagol-Ikapitte I, Watson KJ, Chang S, O'Carroll C, Dey PM, Burstein ES, Dickerson JW, Thompson Gray A, Bubser M, Rook JM, Cho HP, Kramlinger VM, Boutaud O, Jones CK, Conn PJ, Engers DW, Lindsley CW.   +19 more
europepmc   +1 more source

Disarming the Hsp70–Bim Alliance: Small‐Molecule and Peptidic Disruptors of a Chaperone‐Apoptotic Switch in Cancer

ChemistryOpen, EarlyView.
Targeting a nucleotide‐sensitive groove on Hsp70 that binds the Bim BH3 helix, we integrate structures, biophysics, and SAR from peptides, fragments, and phenalene‐dicarbonitrile “wedges.” These disrupt the Hsp70–Bim complex with sub‐µM cellular engagement and in vivo activity while sparing Hsp90/mortalin.
Emadeldin M. Kamel, Mohammed Al‐zharani, Lina M. Alneghery, Noha A. Ahmed, Faris F. Aba Alkhayl, Al Mokhtar Lamsabhi   +5 more
wiley   +1 more source

Mechanism and function of GPR3 regulated by a negative allosteric modulator. [PDF]

Nat Commun
Chen G, Bláhová J, Staffen N, Hübner H, Nunhöfer N, Qiu C, Gmeiner P, Weikert D, Du Y, Xu J.   +9 more
europepmc   +1 more source

Allosteric Regulation of RNA Affinity by Motif V‐VI Coupling in West Nile Virus NS3 Helicase

Proteins: Structure, Function, and Bioinformatics, EarlyView.
ABSTRACT The rise of flaviviral diseases, including West Nile virus (WNV), presents a growing threat to global public health and underscores the urgent need for new therapeutic strategies. The non‐structural protein 3 helicase (NS3h) of the Orthoflavivirus genus, including WNV, is essential for viral replication and a promising antiviral target ...
Priti Roy, Martin McCullagh
wiley   +1 more source

The pathway-independent positive allosteric modulator C1 allows for the identification of active Y₄ receptor relevant positions. [PDF]

Cell Mol Life Sci
Schüß C, Vu O, Pelczyk T, Schubert M, Du Y, Stichel J, Weaver CD, Meiler J, Beck-Sickinger AG.   +8 more
europepmc   +1 more source

AlphaFold2‐Guided Cyclic Peptide Stabilizer Design to Target Protein–Protein Interactions

Proteins: Structure, Function, and Bioinformatics, EarlyView.
ABSTRACT The control and modulation of protein–protein interactions (PPIs) is of central importance for the majority of biological processes and most biomedical applications. Stabilization of PPIs, besides inhibition, is of growing pharmaceutical interest.
Niklas Halbwedl, Martin Zacharias
wiley   +1 more source

Curcumin Derivatives as Allosteric Modulator of α7-nAChR: Functional and Molecular Docking Insights. [PDF]

Med Princ Pract
ElNebrisi E, Ghattas MA, Atatreh N, Hasan S, Oz M.   +4 more
europepmc   +1 more source