Hemophilia

Real-World Evidence-Based Study on Treatment-Free Remission in Chronic Myeloid Leukemia.

BACKGROUND: Treatment-free remission (TFR) has become a treatment goal for chronic myeloid leukemia (CML). This study aimed to define precise conditions for treatment discontinuation and to develop TFR prediction models in a Chinese population. PATIENTS AND METHODS: This study collected data from 11 centers involving 802 cases of tyrosine kinase inhibitor (TKI) discontinuation in patients with CML...

Generative AI-Assisted Discovery of HPK1 Inhibitors.

Generative artificial intelligence (AI) is now widely applied in medicinal chemistry, with detailed case studies emerging in the literature. Here, we describe an early application of REINVENT, AstraZeneca's in-house generative molecular design platform, to identify new inhibitor scaffolds for hematopoietic progenitor kinase 1 (HPK1). REINVENT was deployed at two stages of the project to address di...

From Structure to Selectivity: Integrating CADD and AIDD in Rational Medicinal Chemistry Strategies for DYRK1A Inhibitor Discovery.

Dual specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), a member of the CMGC kinase family, regulates diverse cellular processes and i...

Mapping Non-Homologous Pocket Compatibilities to Identify Hidden Drug-Target Relationships: A Pocket Hopping Framework.

Predicting small molecule-protein interactions across nonhomologous proteins remains challenging because shared ligand recognition is often not eviden...

Recent developments in the therapeutic management of acid-related gastrointestinal diseases.

INTRODUCTION: Acid-related gastrointestinal diseases, particularly gastroesophageal reflux disease (GERD) and peptic ulcer disease (PUD), remain major...

Deep learning reveals FLAD1-mediated mitochondrial metabolic reprogramming in hypoxic tumors.

Hypoxia, a hallmark of solid tumors, drives malignant progression and represents a major therapeutic challenge. Metabolic reprogramming induced by hyp...

Activation of sigma non-opioid intracellular receptor 1 (S1R) receptor inhibits plexin domain containing 2 (Plxdc2) driven microglial inflammation to ameliorate depressive-like behaviours in mice.

BACKGROUND AND PURPOSE: Microglia are central regulators of neuroinflammation in depression. Drivers involved remain incompletely understood. Sigma no...

Unraveling the Mechanism of Drug Binding to SARS-CoV-2 RNA Pseudoknot With Thermodynamics-Driven Machine Learning.

The pseudoknot secondary structure in SARS-CoV-2 RNA is essential for regulating protein synthesis through - $$ - $$ 1 programmed ribosomal frameshi...

Atomic Uncertainty Pinpoints Critical Failure Structures for Trustworthy Molecular Property Prediction.

Accurate prediction of molecular properties is essential for accelerating drug discovery, yet current deep learning methods generally lack reliable un...

Integrative Molecular Scaffold Generation of PI3K/mTOR Inhibitors Using DeepSARM and Ligand-Based Virtual Screening Approaches.

Designing novel core scaffolds for small molecules is an important yet challenging task in medicinal chemistry, particularly during the lead-generatio...

Disease-modifying antirheumatic drugs (DMARDs) for rheumatoid arthritis after failure of biologic or targeted synthetic therapy: a systematic review and network meta-analysis.

RATIONALE: After inadequate response to first-line biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drug (DMARD) therapy in adult...

Chemical features consistently associated with kinase inhibitor activity: a cross-target SHAP analysis under scaffold-split evaluation.

Interpretable machine learning approaches to quantitative structure-activity relationship (QSAR) modelling are increasingly applied in drug discovery,...

A machine learning-driven multitask framework for antibiotic resistance prediction in Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae bloodstream infections among hematological malignancy patients.

BACKGROUND: Inappropriate empirical antimicrobial therapy (IEAT) significantly increases mortality in patients with resistant Gram-negative bacteremia...

Personalized antiplatelet therapy: are we ready for a precision medicine approach.

Dual antiplatelet therapy (DAPT), combining aspirin with a P2Y12 inhibitor, remains central to secondary prevention after acute coronary syndrome and ...

Genotype-Specific Electrophysiological Remodeling in PLN R14del Cardiomyopathy: Implications for Precision Antiarrhythmic Therapy.

BACKGROUND: Inherited PLN (phospholamban) R14del variants cause dilated cardiomyopathy with a high burden of malignant ventricular arrhythmias. Howeve...

Integrated transcriptomic and experimental validation reveal that N‑acetylcysteine ameliorates acute liver failure through multi‑target synergistic regulation of pyroptosis and related signaling networks.

Pyroptosis is a major contributor to the pathophysiology of acute liver failure (ALF), a condition with high mortality. Although N‑acetylcysteine (NAC...

AI-Powered Discovery of Rosmarinic Acid as a Novel Ferroptosis Inhibitor for Ulcerative Colitis via Targeting the ALOX15-VDAC1 Axis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited mechanism-based therapies, and ferroptosis-an iron-dependent lipid peroxi...

Identification of the oxidation stress-related gene signatures and functional verification of MINK1 in prostate cancer cells.

BACKGROUND: A major challenge facing prostate cancer (PCa) cells is oxidative stress, yet the precise role and underlying mechanisms remain inadequate...

Experimental and Mechanistic Validation of PARP1pred for Identifying Potent Leads.

Poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) is a pivotal target for treating homologous recombination-deficient cancers through the mechan...

Smiles-based bioactivity prediction through molecular encoder selection and data augmentation.

Quantitative prediction of inhibitor potency can accelerate early-stage drug discovery. Recently, data-driven approaches have gained widespread intere...