Blog of Signaling Pathways

Allosteric inhibition of HSP70 in collaboration with STUB1 augments enzalutamide efficacy in antiandrogen resistant prostate tumor and patient-derived models

41 views | May 13 2023

The study suggests that targeting HSP70 using small-molecule inhibitors, in combination with ARSI drugs, could be a promising approach to overcome resistance to ARSI in advanced prostate cancer. [Read the Full Post]

LSD1 inhibitors for cancer treatment: Focus on multi-target agents and compounds in clinical trials

38 views | May 13 2023

LSD1 is an epigenetic enzyme overexpressed in many types of cancers, and its inhibitors have emerged as a promising therapeutic strategy for selectively targeting cancer cells while sparing normal cells. [Read the Full Post]

Recent advances of LSD1/KDM1A inhibitors for disease therapy

25 views | May 13 2023

The review highlights recent advances and challenges in LSD1-targeted drug discovery for the treatment of various diseases, including hematologic malignancies. [Read the Full Post]

PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain

37 views | May 13 2023

The study found that LRRK1 is activated by PKC-dependent phosphorylation of a cluster of conserved residues within a region of the CORB domain, which promotes interaction and stabilization of the αC-helix on the kinase domain, revealing a novel activation mechanism. [Read the Full Post]

A Phase Ib Study of Sotrastaurin, a PKC Inhibitor, and Alpelisib, a PI3Kα Inhibitor, in Patients with Metastatic Uveal Melanoma

64 views | May 13 2023

The phase Ib study found that the combination of sotrastaurin and alpelisib was tolerable but showed limited clinical activity in patients with metastatic uveal melanoma or GNAQ/11 mutant cutaneous melanoma. [Read the Full Post]

Incorporating valsartan in sesame oil enriched self-nanoemulsifying system-loaded liquisolid tablets to improve its bioavailability

33 views | May 12 2023

This study developed liquisolid tablets containing a self-nanoemulsifying drug delivery system to improve the solubility and dissolution rate of Valsartan, resulting in increased bioavailability compared to the marketed product. [Read the Full Post]

Subchronic toxicity study of ferric oxide nanoparticles through intragastric administration: A 94-d, repeated dose study in Sprague Dawley rats

29 views | May 12 2023

The study found that Fe2O3 NPs administered through gavage to SD rats for 94 days did not show significant toxicity or adverse effects up to a dose of 500 mg/kg, followed by recovery after Fe2O3 NPs withdrawal for 30 days. [Read the Full Post]

Optimization of the Solvent and In Vivo Administration Route of Auranofin in a Syngeneic Non-Small Cell Lung Cancer and Glioblastoma Mouse Model

29 views | May 12 2023

The study provides important information on the optimal administration route and solvent of auranofin in two syngeneic cancer mouse models, which could contribute to its further development as a potential cancer therapy. [Read the Full Post]

Preferential Solvation Study of Rosuvastatin in the {PEG400 (1) + Water (2)} Cosolvent Mixture and GastroPlus Software-Based In Vivo Predictions

11 views | May 12 2023

The study investigates the solubility and preferential solvation of rosuvastatin in PEG400 + water binary mixtures and predicts that the RST-loaded mixture can enhance the drug's oral absorption and be a promising strategy to control systemic dyslipidemia. [Read the Full Post]

Chronic Inhibition of Toll-Like Receptor 9 Ameliorates Pulmonary Hypertension in Rats

20 views | May 12 2023

TLR9 activation via the NF-κB‒IL-6 pathway contributes to the development of pulmonary hypertension and inhibition of TLR9 may serve as a promising therapeutic approach. [Read the Full Post]

Pharmacological activation of PIEZO1 in human red blood cells prevents Plasmodium falciparum invasion

18 views | May 11 2023

Pharmacological activation of the PIEZO1 channel using Yoda1 and Jedi2 induces echinocytosis, altering the shape and surface area of red blood cells, which prevents efficient invasion by Plasmodium falciparum, providing a potential therapeutic target for malaria prevention. [Read the Full Post]

A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model

27 views | May 11 2023

Bobcat339, a synthetic small molecule that binds to the catalytic pockets of TET proteins, shows potential as a therapeutic for anorexia nervosa and stress-related disorders by inducing TET3 protein degradation and stimulating the expression of AGRP, NPY, and VGAT in a TET3-dependent manner. [Read the Full Post]

DLin-MC3-Containing mRNA Lipid Nanoparticles Induce an Antibody Th2-Biased Immune Response Polarization in a Delivery Route-Dependent Manner in Mice

12 views | May 11 2023

The study investigated the influence of lipid components and immunization route on the humoral immune responses induced by mRNA-based vaccines in mice, highlighting the importance of considering the delivery route when designing and optimizing vaccination strategies. [Read the Full Post]

Intracellular trafficking kinetics of nucleic acid escape from lipid nanoparticles via fluorescence imaging

95 views | May 11 2023

The study investigates the intracellular fate of different lipid nanoparticles for delivering nucleic acids to target cell populations using fluorescence microscopy to determine their localization to endosomes and lysosomes, and demonstrated the technique across different nucleic acid types to aid in the formulation optimization for in vivo studies. [Read the Full Post]

Hematological parameters, antioxidant status, and gene expression of γ-INF and IL-1β in vaccinated lambs fed different type of lipids

17 views | May 11 2023

The study suggests that flaxseed oil had more beneficial effects on the immune response than other vegetable oils in vaccinated lambs. [Read the Full Post]

Non-Nucleoside Inhibitors Decrease Foot-and-Mouth Disease Virus Replication by Blocking the Viral 3Dpol

50 views | May 10 2023

The study used virtual screening and cell-based assays to identify potential inhibitors targeting the RNA-dependent RNA polymerase of Foot-and-mouth disease virus, and identified four compounds with antiviral activity. [Read the Full Post]

Rimegepant 75 mg in Subjects With Hepatic Impairment: Results of a Phase 1, Open-Label, Single-Dose, Parallel-Group Study

34 views | May 10 2023

The study found that rimegepant is not recommended for use in adults with severe hepatic impairment due to a significant increase in systemic exposure observed in this population. [Read the Full Post]

Efficacy, safety and indirect comparisons of lasmiditan, rimegepant, and ubrogepant for the acute treatment of migraine: A systematic review and network meta-analysis of the literature

47 views | May 10 2023

The network meta-analysis found that all formulations of lasmiditan, rimegepant, and ubrogepant were superior in efficacy to placebo, with lasmiditan 200 mg being the most effective but associated with high rates of adverse events. [Read the Full Post]

Mechanical Force Modulates Alveolar Bone Marrow Mesenchymal Cells Characteristics for Bone Remodeling during Orthodontic Tooth Movement through Lactate Production

32 views | May 10 2023

This study suggests that lactate plays a crucial role in controlling bone remodeling-related cellular activities during orthodontic tooth movement, indicating its potential as a therapeutic target for improving orthodontic results. [Read the Full Post]

BC-1215 inhibits ATP-induced IL-1β secretion via the FBXL2-mediated ubiquitination and degradation of not only NLRP3, but also pro-IL-1β in LPS-primed THP-1 cells

42 views | May 10 2023

BC-1215, an inhibitor of FBXO3, suppresses ATP-induced IL-1β secretion in LPS-primed THP-1 cells via the FBXL2-mediated ubiquitination and degradation of NLRP3 and pro-IL-1β, making FBXO3 a potential therapeutic target for inflammatory diseases. [Read the Full Post]