Results 181 to 190 of about 4,995,094 (293)

Artificial Intelligence‐Driven Natural Product Drug Discovery: From Computational Genome Mining to Clinical Translation

Medicinal Research Reviews, EarlyView.
ABSTRACT Natural products (NPs) have historically yielded numerous therapeutic agents, yet their integration into modern drug discovery has been constrained by chemical complexity, low abundance, laborious dereplication, and limited target annotation.
Antonio Lavecchia
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

Developing the Dopamine D3 Receptor (D3R) Antagonist, (R)‐VK4‐116, as a Non‐Opioid Medication for the Treatment of Opioid Use Disorder

Medicinal Research Reviews, EarlyView.
ABSTRACT Opioid use disorder (OUD) remains a major global health challenge, and currently approved treatments (methadone, buprenorphine, and naltrexone) are all opioid receptor‐targeting drugs with limitations in access, adherence, stigma, and use in polysubstance use disorders. Because the dopamine D3 receptor (D3R) is enriched in limbic brain regions
Chia‐Kuei Wu, Yu‐Chih Lin, Junfeng Huang, Bangwei Ding, Pramod Terse, Rahul Nandre, Haksong Jin, Molly Congdon, Kun Shen, Philip Sanderson, Gregory Tawa, Stephanie Mounaud, Marta De Santis, Donald Lo, Elizabeth A. Ottinger, Amy Hauck Newman   +15 more
wiley   +1 more source

Molecular Glue Degraders in Early Development for Cancer Therapy

Medicinal Research Reviews, EarlyView.
ABSTRACT Molecular glue degraders are an emerging class of small molecule allosteric modulators that induce or stabilize protein‐protein interactions, enabling targeted degradation of previously intractable proteins. By redirecting E3 ligases to recognize neosubstrates, proteins that are not typically recognized by a specific E3 ubiquitin ligase, they ...
E. Sila Ozdemir, Hyunbum Jang, Ozlem Keskin, Attila Gursoy, Ruth Nussinov   +4 more
wiley   +1 more source

The positive allosteric modulator GNE-9278 increases gating, conductance, and Ca²⁺ permeability for GluN2D-containing NMDA receptors. [PDF]

Neuropsychopharmacology
Abbott JA, Weaver MG, Liu B, Schwarz SR, Popescu GK.   +4 more
europepmc   +1 more source

Repurposing antimicrobial agents for neuroprotection: Mechanisms, clinical potential, and challenges

Neuroprotection, EarlyView.
Antimicrobial agents exert neuroprotective effects through modulation of interconnected pathways. Tetracyclines, macrolides, antimalarial agents, sulfones, and antiparasitic agents suppress neuroinflammation, oxidative stress, and apoptosis while preserving mitochondrial function and neurotransmission.
Mohammad Amin Manavi, Mohammadreza Salehi, Razieh Mohammad Jafari, Ramin Goudarzi, Saman Khosravi, Ahmad Reza Dehpour   +5 more
wiley   +1 more source

Distinct Conformational Switches Control WPD‐Loop Dynamics Across Protein Tyrosine Phosphatase Subfamilies

Proteins: Structure, Function, and Bioinformatics, EarlyView.
ABSTRACT Protein Tyrosine Phosphatases (PTPs) regulate cellular signaling by balancing phosphotyrosine levels through a conserved WPD‐loop that switches between open (inactive) and closed (active) conformations. While this conformational change is crucial for catalysis, the structural factors governing this motion remain poorly understood.
Colin L. Welsh, Lalima K. Madan
wiley   +1 more source

The Histidine 382 Residue Influences the Thermal Stability and Binding Propensity of the E2 Domain of Amyloid Precursor Protein

Proteins: Structure, Function, and Bioinformatics, EarlyView.
ABSTRACT The E2 domain of amyloid precursor protein (APP_E2) plays a central role in the protein's function. We reinvestigate how the missense mutation, ΔH382L, affects the domain's thermal stability and ligand binding propensity through differential scanning fluorometry.
Sphamandla Ndlovu, Candice Ngubane, Zamaxasibe Nxele, Raymond Hewer, Alexandré Delport   +4 more
wiley   +1 more source

Temporal Hydrogen‐Bond Network Analysis Reveals Substrate‐Directed Connectivity in Dihydrofolate Reductase

Proteins: Structure, Function, and Bioinformatics, EarlyView.
ABSTRACT Hydrogen‐bond networks are central to protein function, but most network analyses rely on static representations that neglect how interactions evolve in time. Here, we introduce a framework that combines instantaneous and temporal graph analysis of hydrogen‐bond networks derived from molecular dynamics (MD) trajectories to quantify ligand ...
Tandac F. Guclu, Canan Atilgan, Ali Rana Atilgan   +2 more
wiley   +1 more source

Discovery, Characterization, and Optimization of a Novel Positive Allosteric Modulator-Antagonist of the D₃ Dopamine Receptor. [PDF]

J Med Chem
Moritz AE, Wang F, Madaras NS, Kelley AM, Snyder KK, Gandhi D, Inbody LR, Akano EO, Shi L, Lane JR, Free RB, Frankowski KJ, Sibley DR.   +12 more
europepmc   +1 more source