China Pharmaceutical University

Electronic tuning of dynamic imine bonds enables programmable pore gating in metal–organic frameworks

Metal–organic frameworks (MOFs) are promising host matrices for molecular encapsulation, yet their application is often limited by fixed pore apertures that exclude guest molecules larger than the pore openings. Herein, we overcome this limitation by electronic tuning of dynamic...

Medicinal Chemistry Strategies for Targeting RNA-Binding Proteins: Design, Optimization, and Therapeutic Potential

Abstract RNA-binding proteins (RBPs) are essential regulators of post-transcriptional gene expression whose disruption contributes broadly to tumor initiation, progression, and therapeutic resistance. Through their control of RNA splicing, stability, translation, and epitranscrip...

Discovery of Tricyclic Oxazinoquinolinone-Based BCL6 PROTAC Degraders with Potent Activity Against Diffuse Large B-Cell Lymphoma

Abstract B-cell lymphoma 6 (BCL6) is a key transcriptional repressor involved in the pathogenesis of diffuse large B-cell lymphoma (DLBCL). In this study, scaffold hopping of BI-3802 led to compound 1, a new tricyclic BCL6-targeting ligand. Further optimization of linker architec...

Atroposelective Synthesis of Axially Chiral Diaryl Ethers via Organocatalyzed Enantioselective Desymmetric Allyl Addition

Catalytic asymmetric construction of C─O axially chiral diaryl ethers remains underdeveloped relative to C─C biaryl atropisomers, and examples that simultaneously create a stereogenic carbon center are scarce. Herein, we report a chiral phosphoric acid‐catalyzed enantioselective...

Preparation and Investigation of Solvatomorphs of Anti-Tumor Candidate RA-XII

RA-XII, a unique natural cyclopeptide, is a potential anti-colorectal cancer candidate by mainly inhibiting protective autophagy, SREBP-1-dependent lipid biogenesis and suppressing activation of the Akt-mTOR pathway in HCT-116 cells. However, there have been no investigations int...

Insights into HIF Prolyl Hydroxylase Inhibitors: Recent Advances and Expanding Therapeutic Applications beyond Anemia

Abstract Oxygen homeostasis is fundamental to cellular and organismal physiology and is primarily governed by the hypoxia-inducible factor (HIF) signaling pathway. Within this pathway, prolyl hydroxylase domain enzymes (PHDs) serve as a key oxygen sensor that regulates HIF-α stab...

Systematic review and network meta-analysis of interventions for adults with simple obesity: Study protocol

Obesity has become a major global public health challenge, and its rising prevalence contributes to substantial health and economic burdens. Existing systematic reviews are largely confined to a single intervention category or to mixed populations, which limits targeted recommend...

Harnessing the Silicon Effect for Copper-Catalyzed Linear- E -Selective Reductive Coupling of Ketones with Allenylsilanes

Abstract We report a copper-catalyzed reductive coupling of ketones with allenylsilanes that delivers γ-silyl homoallylic alcohols with exceptional linear E-selectivities. Mechanistic investigations indicate that the silyl substituent functions as a directing element for regiosel...

ProDTI: Prior-Guided Positive-Unlabeled Learning for Robust Drug-Target Interaction Prediction

Abstract Motivation Accurate Drug-Target Interaction (DTI) prediction is critical for drug discovery. While deep learning advances this field, the fundamental lack of verified negative interactions inevitably causes biased risk estimation. Although formulating DTI prediction as a...

Intestinal FXR agonism synergizes with leptin to improve obesity by reducing appetite via secretin

Abstract Obesity is a chronic condition and is closely associated with various metabolic diseases. It has become a global health concern, and effective pharmacotherapies are urgently needed. Farnesoid X receptor (FXR) is widely regarded as a pivotal target for the treatment of me...

Astragaloside IV improves MASLD via GCN5-LXRα/SREBP1c signaling pathway-mediated hepatic de novo lipogenesis

BACKGROUND: Astragaloside IV (AS-IV), a bioactive saponin from Astragalus membranaceus, shows promise for treating metabolic dysfunction-associated steatotic liver disease (MASLD), though its mechanisms remain unclear. PURPOSE: This study aimed to elucidate how AS-IV alleviates h...

Engineered Peptide Self‐Assembled Nanofibers for Enhanced STING Activation: A Promising Nanodelivery Platform for Immunotherapy of Pediatric Solid Tumors

ABSTRACT STING agonists (e.g., cGAMP), which function as immunotherapeutic agents activating the stimulator of interferon genes (STING) pathway, hold promise for treating pediatric solid tumors including neuroblastoma. However, their clinical translation is hindered by limitation...

Engineered Allosteric Biosensor for In Situ DNA Glycosylase Detection in Neuroblastoma Risk Stratification and Drug Resistance Monitoring

ABSTRACT Accurate and in situ detection of uracil‐DNA glycosylase (UDG) is crucial for clinical diagnosis and prognosis assessment. However, conventional methods show low accuracy, limited sensitivity, and off‐target signal leakage due to flawed signal input/output and amplificat...

Demethylzeylasteral Targets the Sp1/AGAP2 Axis to Impair Autophagic Flux and Induce Apoptosis in Hepatic Stellate Cells

ABSTRACT Background and Aim Chronic liver injury‐induced liver fibrosis, if left untreated, can progress to cirrhosis or hepatocellular carcinoma, posing a serious threat to human health. Our previous study demonstrated that the natural product demethylzeylasteral (T‐96) alleviat...

NAT-A exhibits anti-tumor activity against acquired epidermal growth factor receptor- tyrosine kinase inhibitor-resistant non-small cell lung cancer via inhibiting the β-catenin/PKM2 axis

Hyperactivation of the Wnt/β-catenin pathway is a key driver of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance in non-small cell lung cancer (NSCLC), with pyruvate kinase M2 (PKM2) serving as a critical transcriptional coactivator of β -catenin....

A Modular (1,3-Oxathiolan-2-yl)ethoxy Trigger Unlocks Activatable Probes for In Vivo Imaging of Hypobromous Acid

Abstract Hypobromous acid (HOBr) is a critical reactive oxygen species in inflammatory pathology; however, tracking its dynamics in vivo remains a formidable challenge. Herein, we report a convenient, sensitive and selective (1,3-oxathiolan-2-yl)ethoxy (OTE) recognition moiety fo...

Post-Competitive Interface Reprogramming for Amplified Multiplex Bacterial Fingerprinting in Biofluids

Abstract Low-burden bacterial infections demand rapid and reliable pathogen fingerprinting, yet cross-reactive sensor arrays remain limited by weak and overlapping optical signatures. Here we introduce postcompetitive interface reprogramming (PCIR), a sensor-array strategy that e...

NBS ‐Mediated Mitsunobu Glycosylation: Facile Assembly of N ‐Glycosides from Unprotected Sugars and Application to Polysaccharide Analysis

Comprehensive Summary Chemical N ‐glycosylation is a crucial step in the synthesis of complex N ‐glycosides, particularly nucleosides. However, traditional carbohydrate chemistry often relies heavily on protecting groups, which can lead to cumbersome, time‐consuming substrate pre...

Discovery of Potent and Selective VHL-Recruiting PROTAC Degraders Targeting EGFR with Improved Developability and Potent Anti-NSCLC Efficacy

Abstract Epidermal growth factor receptor (EGFR) kinase inhibitors have revolutionized non-small cell lung cancer (NSCLC) treatment; however, the inevitable acquired resistance necessitates alternative strategies beyond conventional inhibition. Herein, we report the discovery and...

A Microneedle Platform Co-loaded with Eugenol, Chlorogenic Acid, and Allopurinol for In Vivo Modulation of Pathological Crystal Formation in Experimental Gouty Arthritis

Abstract Gouty arthritis arises from pathological deposition of monosodium urate (MSU) crystals, whose interactions with surrounding tissues initiate and amplify inflammation. Here, we developed a nanoengineered microneedle (MN) platform for localized modulation of pathological c...