Molecular Pharmacology
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Some drugs 'fail' because of unrealistic testing conditions, scientists discover
Some drugs 'fail' because of unrealistic testing conditions, scientists discover Sadie Harley Scientific Editor Robert Egan Associate Editor A drug once dismissed as ineffective suddenly worked—when scientists tested it under more realistic conditions that mimic the human body. In this surprising new discovery, Northwestern University scientists uncovered a hidden rule of drug behavior. A medicine's effectiveness can change dramatically depending on the conditions inside our cells.
Diverse binding poses of agonistic neurotoxins on human Na<sub>v</sub>1.6
Abstract Voltage-gated sodium (Nav) channels are key targets of various venomous toxins. Deciphering the binding poses and mechanisms of action of representative toxins will help to dissect the functional mechanism of the channels and facilitate therapeutic development targeting Nav channels1,2. Here we present cryo-electron microscopy (cryo-EM) structures of distinct binding poses of three agonistic peptide toxins on the human Nav1.6–β1 channel complex.
Scientists found a new Alzheimer’s trigger and a drug that stops it
Scientists found a new Alzheimer’s trigger and a drug that stops it - Date: - June 8, 2026 - Source: - ETH Zurich - Summary: - Researchers have identified a new Alzheimer’s target and created an experimental compound that blocks a damaging process inside brain cells. In mice, the treatment slowed nerve cell loss, reduced Alzheimer’s-related changes, and even appeared to promote healthier aging. - Share: A promising experimental compound developed by researchers at ETH Zurich could offer a...
What is glioblastoma and why is it so hard to treat?
Glioblastoma is one of the deadliest cancers — why is it so hard to treat? Mon 8 Jun 2026 at 2:01pm The death of former Australian of the Year Richard Scolyer overnight came after a multi-year fight with one of the most difficult to treat cancers. Glioblastoma is known as the most aggressive form of brain cancer.
Comprehensive characterization of skeletal muscle remodeling in hSOD1G93A mice reveals limited functional impact of systemic FOXO1 inhibition
Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron (MN) loss, muscle atrophy and paralysis. Although traditionally considered a MN-specific disease, accumulating evidence supports a crucial contribution of skeletal muscle pathology to disease onset and progression. Except for specific mutations, to date there is no effective treatment for ALS.
What Molecular Structure Cannot Tell Us: A Taxonomy of Explainability Gaps in GNN-Based Drug Toxicity Prediction
arXiv:2605.26183v2 Announce Type: replace-cross Abstract: Not all clinically relevant adverse effects are structurally inferable from molecular graphs - regardless of model quality or architectural complexity. This study introduces an operational taxonomy of the structural information limits that prevent structure-based toxicity prediction, independent of the learning algorithm employed. Graph Neural Networks (GNNs) have emerged as a natural approach for molecular toxicity prediction,...
O-GlcNAc transferase regulates H2O2 production via p38 MAPK
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by augmented transforming growth factor-{beta} (TGF-{beta}) signaling leading to excessive extracellular matrix (ECM) deposition. The fibroblast-to-myofibroblast-transition (FMT) and metabolic reprogramming of lung fibroblasts (HLFs) are essential to IPF pathogenesis, yet the connection between nutrient metabolism and fibrogenesis remains poorly defined. The O-linked N-acetylglucosamine (O-GlcNAc)...
(2R,6R)-Hydroxynorketamine elicits rapid antidepressant effects by promoting astrocytic μ-δ opioid receptor heterodimerization
Ketamine produces rapid antidepressant effects but is constrained by psychotomimetic properties and abuse potential. The ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) shows antidepressant-like efficacy without N-methyl-D-aspartate receptor (NMDAR) blockade, yet its upstream targets remain unclear. Here we show that HNK potentiates hippocampal excitatory transmission and reverses stress-induced behavioural deficits through opioid receptor signaling.
Genotype-Conditioned Molecular Generation via Evidence-Grounded Multi-Objective Latent Perturbation in Diffusion Models
arXiv:2606.01461v1 Announce Type: new Abstract: Developing effective anticancer therapeutics remains challenging due to tumor heterogeneity and the absence of well-defined molecular targets across cancer subtypes. Generative models conditioned on cancer genotypes offer a promising avenue for personalized drug discovery, yet existing approaches lack explicit optimization for simultaneous sensitivity, synthesizability, and mechanistic binding plausibility.
Cell free-mtDNA release drives pyroptosis and inflammation in cell models carrying the mitochondrial m.3243A>G pathogenic variant
Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) syndrome is primarily caused by the heteroplasmic m.3243A>G/MT-TL1 pathogenic variant. Patients exhibit elevated circulating cell-free mtDNA (cf-mtDNA) in plasma, which acts as a damage-associated molecular pattern. Using patient-derived fibroblasts and neuronal progenitors, as well as transmitochondrial cytoplasmic hybrids (cybrids), we show that mutant cells release higher levels of cf-mtDNA than wild-type...