Blog of Signaling Pathways

Autocrine EGF and TGF-α promote primary and acquired resistance to ALK/c-Met kinase inhibitors in non-small-cell lung cancer

19 views | Nov 29 2023

Increased autocrine production of EGF and TGF-α mediates both primary and acquired resistance to ALK and c-MET inhibitors in non-small-cell lung cancer, suggesting a potential therapeutic strategy involving combination treatments with EGFR inhibitors. [Read the Full Post]

Neutrophil-Specific Syk Expression Is Crucial for Skin Disease in Experimental Epidermolysis Bullosa Acquisita

21 views | Nov 29 2023

Syk inhibition in neutrophils emerges as a pivotal therapeutic approach for epidermolysis bullosa acquisita, preventing skin disease triggered by anti-C7 antibodies and indicating potential treatment strategies. [Read the Full Post]

Inhibition of Mertk Signaling Enhances Bone Healing after Tooth Extraction

34 views | Nov 29 2023

Targeting Mertk, a specific TAM receptor, enhances bone regeneration after tooth extraction, offering a potential therapeutic approach for improving outcomes in cases where the regenerative process is impaired. [Read the Full Post]

Entropy driven cooperativity effect in multi-site drug optimization targeting SARS-CoV-2 papain-like protease

13 views | Nov 28 2023

The study investigated the enhanced binding affinity between the papain-like protease (PLpro) of SARS-CoV-2 and the existing drug GRL0617, revealing that optimization of specific regions in the drug led to increased cooperativity by stabilizing key residues and reducing entropic loss, providing valuable insights for drug development strategies targeting PLpro. [Read the Full Post]

Imidazole-4-N-acetamide Derivatives as a Novel Scaffold for Selective Targeting of Cyclin Dependent Kinases

33 views | Nov 28 2023

The study explored imidazole-4-N-acetamide substituted derivatives of the pan-CDK inhibitor PHA-793887 and demonstrated a strong correlation between calculated binding parameters using non-equilibrium thermodynamics and inhibitory potencies in in vitro kinase assays, highlighting the method's effectiveness in predicting the activity of potential anticancer drug candidates. [Read the Full Post]

The Subtilisin-Like Protease Furin Regulates Hemin-Dependent Ectodomain Shedding of Glycoprotein VI

17 views | Nov 28 2023

This study reveals a previously unrecognized mechanism where hemin induces shedding of the GPVI ectodomain through furin-mediated pathways, enhancing platelet activation and thrombus formation, thus providing crucial insights into hemin-induced thrombotic disorders. [Read the Full Post]

Pharmacological inhibition of TBK1/IKKε blunts immunopathology in a murine model of SARS-CoV-2 infection

40 views | Nov 28 2023

In this study, researchers discovered that the small molecule idronoxil inhibits TBK1/IKKε signaling, attenuating hyper-inflammation in SARS-CoV-2-challenged mice and establishing a critical role for TBK1/IKKε signaling in severe COVID-19 pathology. [Read the Full Post]

BMS-265246, a Cyclin-Dependent Kinase Inhibitor, Inhibits the Infection of Herpes Simplex Virus Type 1

15 views | Nov 28 2023

BMS-265246 (BMS), a cyclin-dependent kinase (CDK) 1/2 inhibitor, has been identified as a potent anti-HSV-1 agent, effectively limiting viral multiplication in various cell lines and interfering with multiple stages of the HSV-1 replication process. [Read the Full Post]

Indication for a Pneumocystis Prophylaxis Therapy in Patients with Vascular Anomalies Treated with PIK3/AKT/mTOR Pathway Inhibitors: Experts' Opinion and Systematic Review from the Literature

24 views | Nov 27 2023

The study underscores the rare but existing risk of Pneumocystis jirovecii pneumonia in patients with vascular anomalies treated with mTOR inhibitors, indicating the potential benefit of prophylaxis, particularly with trimethoprim-sulfamethoxazole, for specific high-risk patient groups. [Read the Full Post]

Human phytanoyl-CoA dioxygenase domain-containing 1 (PHYHD1) is a putative oxygen sensor associated with RNA and carbohydrate metabolism

19 views | Nov 27 2023

PHYHD1, a 2-oxoglutarate-dependent dioxygenase, exhibits inhibitory interactions with succinate and fumarate, activation by citrate, binds mRNA, and is localized in both the nucleus and cytoplasm, implicating it as a potential oxygen sensor and linking it to diverse cellular processes including cell division, RNA metabolism, and carbohydrate metabolism. [Read the Full Post]

Cytoplasmic Hsp70s promote EcR transport into the nucleus by responding to various stimuli

59 views | Nov 27 2023

This study reveals that cytoplasmic Hsp70s facilitate the transport of the ecdysone receptor (EcR) into the nucleus in response to diverse stimuli, shedding light on the intricate mechanisms underlying insect metamorphosis and highlighting potential applications in pest control and broader biological research. [Read the Full Post]

Indole derivatives targeting colchicine binding site as potential anticancer agents

35 views | Nov 27 2023

Research on indole derivatives targeting the colchicine-binding site (CBS) of microtubules holds significant promise for the development of novel and effective anticancer therapies with improved efficacy and reduced toxicity. [Read the Full Post]

Overfit deep neural network for predicting drug-target interactions

107 views | Nov 27 2023

The OverfitDTI framework utilizes intentionally overfitted deep neural networks to accurately capture the intricate relationships between drugs and targets, enabling precise drug-target interaction predictions, as demonstrated by the successful identification and experimental validation of TEK inhibitors. [Read the Full Post]

Salt-inducible kinase inhibition promotes the adipocyte thermogenic program and adipose tissue browning

10 views | Nov 26 2023

The study reveals that SIK3 functions as a crucial phosphorylation switch for β-adrenergic activation, driving the adipose tissue thermogenic program, offering potential therapeutic avenues for obesity and related cardiometabolic diseases. [Read the Full Post]

Splenic monocytes mediate inflammatory response and exacerbate myocardial ischemia/reperfusion injury in a mitochondrial cell-free DNA-TLR9-NLRP3-dependent fashion

10 views | Nov 26 2023

The study demonstrates that splenic NLRP3 inflammasome activation shortly after reperfusion onset, triggered by mitochondrial cell-free DNA and Toll-like receptor 9-dependent mechanisms, exacerbates myocardial ischemia/reperfusion injury. [Read the Full Post]

TTK Protein Kinase promotes temozolomide resistance through inducing autophagy in glioblastoma

40 views | Nov 26 2023

Inhibition of TTK Protein Kinase (TTK) using specific inhibitors, in combination with Temozolomide (TMZ) chemotherapy, overcomes TMZ resistance in glioblastoma multiforme (GBM) cells by suppressing autophagy, suggesting a promising therapeutic strategy for improving treatment outcomes in GBM patients. [Read the Full Post]

Inhibition of Diacylglycerol Acyltransferase 2 Versus Diacylglycerol Acyltransferase 1: Potential Therapeutic Implications of Pharmacology

29 views | Nov 26 2023

DGAT2 inhibitors, exemplified by ervogastat, offer a promising and well-tolerated therapeutic approach for patients with nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and NASH with liver fibrosis, in contrast to limited efficacy and adverse effects associated with DGAT1 inhibitors. [Read the Full Post]

Microglia trigger the structural plasticity of GABAergic neurons in the hippocampal CA1 region of a lipopolysaccharide-induced neuroinflammation model

18 views | Nov 26 2023

The study demonstrates that LPS-induced microglial activation in the hippocampal CA1 region leads to cognitive impairment through the upregulation of GABAergic inhibitory synapses, and this effect can be reversed by blocking GABA receptor activity or depleting microglia, highlighting the critical role of neuroinflammatory responses and synaptic plasticity in cognitive dysfunction. [Read the Full Post]

Revisiting matrix hydrogel composed of gelatin and hyaluronic acid and its application in cartilage regeneration

28 views | Nov 25 2023

The biomacromolecule-based bioadhesive matrix hydrogel, composed of methacrylate gelatin and modified hyaluronic acid, demonstrates promising potential for cartilage repair by promoting tissue integration, supporting chondrogenesis of stem cells, and enhancing articular cartilage regeneration in knee osteoarthritis. [Read the Full Post]

High-intensity interval training improves fatty infiltration in the rotator cuff through the β3 adrenergic receptor in mice

26 views | Nov 25 2023

High-Intensity Interval Training (HIIT) improved muscle quality in a rotator cuff tear model by activating the β3 adrenergic receptor pathway, enhancing supraspinatus muscle function, and reducing atrophy and fatty infiltration. [Read the Full Post]