Blog of Signaling Pathways

Safety of HIF prolyl hydroxylase inhibitors for anemia in dialysis patients: a systematic review and network meta-analysis

36 views | Sep 18 2023

The systematic review and network meta-analysis found that hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) did not significantly differ from erythropoiesis-stimulating agents (ESAs) in terms of overall adverse events and serious adverse events, but differences were observed in gastrointestinal disorder, hypertension, vascular-access complications, and hemoglobin response. [Read the Full Post]

Synthesis and Preclinical Evaluation of a Novel Fluorine-18-Labeled Tracer for Positron Emission Tomography Imaging of Bruton's Tyrosine Kinase

44 views | Sep 18 2023

[18F]PTBTK3, a PET radiotracer based on a selective BTK inhibitor, demonstrates BTK-dependent tumor uptake in BTK-positive tumors, showing promise for the diagnosis and development of BTK-targeted therapies. [Read the Full Post]

Remibrutinib inhibits hives effector cells stimulated by serum from chronic urticaria patients independently of FcεR1 expression level and omalizumab clinical response

71 views | Sep 18 2023

Remibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, effectively inhibits the activation of basophils and mast cells induced by serum from chronic urticaria patients, regardless of their responsiveness to omalizumab treatment. [Read the Full Post]

Acetylation regulates the nucleocytoplasmic distribution and oncogenic function of karyopherin alpha 2 in lung adenocarcinoma

95 views | Sep 18 2023

The acetylation of KPNA2 by CBP/p300 promotes cytosolic localization and suppresses its oncogenic activity in lung cancer cells. [Read the Full Post]

Novel Therapies in Plaque Psoriasis: A Review of Tyrosine Kinase 2 Inhibitors

76 views | Sep 18 2023

Deucravacitinib, an allosteric tyrosine kinase 2 inhibitor, has been approved as a first-in-class treatment for moderate-to-severe plaque psoriasis and shows improved safety compared to orthosteric Janus kinase inhibitors. [Read the Full Post]

An injectable superior depot of Telratolimod inhibits post-surgical tumor recurrence and distant metastases

61 views | Sep 17 2023

The development of an injectable phase transition gel (PGE) for the delivery of Telratolimod (Tel) enhances the immunotherapeutic effects while reducing the risk of adverse effects, providing a clinically available option for effective postoperative combined therapy. [Read the Full Post]

Iron Chelator VLX600 Inhibits Mitochondrial Respiration and Promotes Sensitization of Neuroblastoma Cells in Nutrition-Restricted Conditions

77 views | Sep 17 2023

The iron chelator VLX600 inhibits mitochondrial respiration, reduces MYCN/LMO1 expression, and induces cell death in neuroblastoma cells, regardless of MYCN status, suggesting its potential as a therapeutic agent in combination with conventional chemotherapy for the treatment of neuroblastoma. [Read the Full Post]

Discovery of ATR kinase inhibitor berzosertib (VX-970, M6620): Clinical candidate for cancer therapy

102 views | Sep 17 2023

VX-970 (berzosertib or M6620) is a promising small-molecule ATR inhibitor that shows potential as an effective anticancer drug, both as monotherapy and in combination with chemotherapy or radiotherapy strategies, based on preclinical data and ongoing phase I/II clinical trials. [Read the Full Post]

Selective inhibition of ATM-dependent double-strand break repair and checkpoint control synergistically enhances the efficacy of ATR inhibitors

99 views | Sep 17 2023

Inhibition of ATR kinase and simultaneous suppression of ATM kinase synergistically enhance cancer cell death and show promise as a novel combination approach for cancer therapy. [Read the Full Post]

Evaluation of Drug-Drug Interaction Potential of Enarodustat (JTZ-951) Using a Cytochrome P450 Probe Cocktail

67 views | Sep 17 2023

Enarodustat, administered at doses of 25 mg and 50 mg, showed minimal to no significant drug interactions with cytochrome P450 enzymes 1A2, 2C9, 2C19, 2D6, and 3A4 in a phase 1 multiple-ascending-dose study, with changes in geometric mean ratios generally being less than 2-fold. [Read the Full Post]

Phase 1 study of oral selective estrogen receptor degrader (SERD) amcenestrant (SAR439859), in Japanese women with ER-positive and HER2-negative advanced breast cancer (AMEERA-2)

18 views | Sep 16 2023

The AMEERA-2 study found that amcenestrant 400 mg QD demonstrated favorable safety and efficacy, leading to its selection as the recommended Phase II dose for monotherapy in a larger clinical trial for metastatic breast cancer. [Read the Full Post]

Modeling the Effect of Cooperativity in Ternary Complex Formation and Targeted Protein Degradation Mediated by Heterobifunctional Degraders

60 views | Sep 16 2023

This study develops a pharmacodynamic model and statistical inference model to investigate the role of cooperativity in ternary complex formation and degradation efficiency, providing insights for the rational design of effective HBF degraders in targeted protein degradation. [Read the Full Post]

A small molecule G6PD inhibitor reveals immune dependence on pentose phosphate pathway

82 views | Sep 16 2023

The study developed a small molecule inhibitor, G6PDi-1, that effectively targets the glucose-6-phosphate dehydrogenase (G6PD) enzyme and modulates immune responses by depleting NADPH and inhibiting inflammatory cytokine production in T cells while suppressing respiratory burst in neutrophils. [Read the Full Post]

The Microtubule Destabilizer Eribulin Synergizes with STING Agonists to Promote Antitumor Efficacy in Triple-Negative Breast Cancer Models

25 views | Sep 16 2023

Eribulin, a microtubule destabilizer used in the treatment of triple-negative breast cancer, has been found to enhance interferon beta expression and innate immune sensing pathways when combined with STING agonists, suggesting its potential as an immune adjuvant in combination with immunotherapies for more effective treatment of TNBC and other malignancies. [Read the Full Post]

BRAF v600E-mutant cancers treated with vemurafenib alone or in combination with everolimus, sorafenib, or crizotinib or with paclitaxel and carboplatin (VEM-PLUS) study

67 views | Sep 16 2023

The VEM-PLUS study found that combining vemurafenib with cytotoxic chemotherapy or RAF- or mTOR-targeting agents did not significantly improve overall survival or progression-free survival compared to vemurafenib monotherapy in patients with solid tumors harboring BRAF V600E mutations. [Read the Full Post]

Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1

20 views | Sep 15 2023

Pre-clinical studies demonstrate that monotherapy with a Menin inhibitor (MI) induces clinical remissions in some relapsed/refractory AML patients, but the combination of MI with inhibitors targeting BRD4, MOZ, LSD1, or CBP/p300 shows synergistic effects and superior efficacy, suggesting potential strategies to overcome therapy resistance and prevent relapse. [Read the Full Post]

[Decursin affects proliferation, apoptosis, and migration of colorectal cancer cells through PI3K/Akt signaling pathway]

15 views | Sep 15 2023

Decursin inhibits proliferation, induces apoptosis, suppresses migration, and regulates epithelial-mesenchymal transition in colorectal cancer cells through downregulation of the PI3K/Akt pathway and modulation of key proteins involved in cell survival, apoptosis, and cell-cell adhesion. [Read the Full Post]

Semi-quantification and Potency Verification of the HIV Protease Inhibitor Based on the Matrix-Capsid Protein Immobilized Nickel (II)/NTA-Tol/Graphene Oxide/SPCE Electrochemical Biosensor

38 views | Sep 15 2023

The study proposes a low-cost electrochemical biosensor platform for the semi-quantification and verification of HIV protease inhibitors, offering a potential solution to expedite the discovery and development of new HIV drugs. [Read the Full Post]

Indirect treatment comparison of lurbinectedin versus other second-line treatments for small-cell lung cancer

35 views | Sep 15 2023

Lurbinectedin showed superior survival benefit and a favorable safety profile compared to other second-line treatments for platinum-sensitive small-cell lung cancer (SCLC). [Read the Full Post]

Metabolic Flux Analysis Reveals the Roles of Stearate and Oleate on CPT1C-mediated Tumor Cell Senescence

26 views | Sep 15 2023

The study demonstrates that manipulating the stearate/oleate ratio through inhibition of SCD-1, along with depletion of CPT1C, could be a promising strategy for cancer therapy by inducing tumor cell senescence and inhibiting proliferation. [Read the Full Post]