Blog of Signaling Pathways

Early changes in circulating cell free KRAS G12C predicts response to adagrasib in KRAS mutant non-small cell lung cancer patients

94 views | Sep 06 2023

Early changes in circulating tumor DNA (ctDNA) levels of KRAS G12C, assessed approximately three weeks into treatment, can predict the likelihood of a favorable objective clinical response in patients with advanced, KRAS G12C mutant lung cancer. [Read the Full Post]

The Therapeutic Landscape for KRAS-Mutated Colorectal Cancers

53 views | Sep 06 2023

The development of selective inhibitors targeting KRAS mutations, such as the FDA-approved Sotorasib and Adagrasib, has shown promise in treating colorectal cancer, but further research is needed to optimize their efficacy and overcome treatment resistance. [Read the Full Post]

Two is company, is three a crowd? Triplet therapy, novel molecular targets, and updates on the management of advanced renal cell carcinoma

69 views | Sep 06 2023

Recent advances in the management of advanced renal cell carcinoma include the favorability of nivolumab plus cabozantinib in combination therapy, promising results from triplet therapy and HIF-2α inhibitors, investigation of metabolic pathway inhibitors and biomarkers, and the ongoing evaluation of cytoreductive nephrectomy in the context of combination therapy. [Read the Full Post]

Effects of the inclusion of coffee pulp silage in the diet on the performance and profitability of crossbred milk cows in the middle tropics

45 views | Sep 06 2023

The inclusion of coffee pulp silage in the diet of crossbred dairy cows in the middle tropics improved their productive efficiency and nutritional characteristics without affecting milk production. [Read the Full Post]

H1N1 influenza virus infection through NRF2-KEAP1-GCLC pathway induces ferroptosis in nasal mucosal epithelial cells

70 views | Sep 06 2023

This study reveals that the H1N1 virus induces ferroptosis in human nasal epithelial cells via the NRF2-KEAP1-GCLC signaling pathway and glutaminolysis, contributing to nasal mucosal epithelial inflammation and suggesting a potential therapeutic target for viral-induced nasal inflammation. [Read the Full Post]

Exosomes secreted from cardiomyocytes suppress the sensitivity of tumor ferroptosis in ischemic heart failure

73 views | Sep 05 2023

Myocardial infarction-induced exosomes containing miR-22-3p derived from cardiomyocytes suppress ferroptosis and decrease the sensitivity of tumor cells to ferroptosis inducers, suggesting the potential of targeting exosome-mediated communication as a novel therapeutic strategy for antitumor therapy. [Read the Full Post]

ATP-citrate lyase inhibitor improves ectopic lipid accumulation in the kidney in a db/db mouse model

72 views | Sep 05 2023

The ACL inhibitor BMS-303141 effectively attenuated ectopic lipid accumulation and improved renal injuries in db/db mice, suggesting its potential as a therapeutic treatment for obesity-related renal complications. [Read the Full Post]

Deuterium in drug discovery: progress, opportunities and challenges

114 views | Sep 05 2023

Deuteration, the substitution of a hydrogen atom with its heavy isotope deuterium, has emerged as a promising strategy in drug discovery and development, offering the potential to enhance drug efficacy and safety through improved pharmacokinetic and toxicity profiles. [Read the Full Post]

Clinical Utility of Deucravacitinib for the Management of Moderate to Severe Plaque Psoriasis

82 views | Sep 05 2023

Deucravacitinib, a first-in-class TYK2 small molecule inhibitor, shows significant clinical efficacy and a favorable safety profile in the treatment of moderate-to-severe psoriasis based on a systematic review and meta-analysis of randomized controlled trials. [Read the Full Post]

[LLY-283 inhibits proliferation and metastasis of head and neck squamous cell carcinoma by targeting PRMT5]

20 views | Sep 05 2023

LLY-283, by inhibiting PRMT5 expression, effectively suppresses the proliferation and metastasis of Head and Neck Squamous Cell Carcinoma (HNSCC) and reduces tumor growth in vivo. [Read the Full Post]

Genomic and biological aspects of resistance to selective poly(ADP-ribose) glycohydrolase inhibitor PDD00017273 in human colorectal cancer cells

20 views | Sep 04 2023

The study identified specific mutations in PARG and PARP1, resulting in structural modifications and downregulation of PARP1, leading to resistance to the PARG inhibitor PDD00017273 in HCT116RPDD cells. [Read the Full Post]

CDK7 controls E2F- and MYC-driven proliferative and metabolic vulnerabilities in multiple myeloma

52 views | Sep 04 2023

In pre-clinical studies, therapeutic targeting of CDK7 using the covalent small molecule inhibitor YKL-5-124 has shown promising results by inhibiting E2F and MYC transcriptional programs, impairing glycolysis, and inducing tumor regression in multiple myeloma mouse models. [Read the Full Post]

A new hazard assessment workflow to assess soil contamination from large and artisanal scale gold mining

80 views | Sep 04 2023

The study developed a new workflow model combining spatial mapping, compositional analysis, and geostatistical modeling to identify and assess the contamination levels and potential risks associated with artisanal and small-scale gold mining activities in the Kedougou region, emphasizing the need for comprehensive risk assessments and improved regulation. [Read the Full Post]

Serine/threonine kinase TBK1 promotes cholangiocarcinoma progression via direct regulation of β-catenin

49 views | Sep 04 2023

TBK1 shows increased expression in cholangiocarcinoma and promotes tumor growth and metastasis by interacting with β-catenin, suggesting its potential as a prognostic biomarker and therapeutic target. [Read the Full Post]

Microglia mediate neurocognitive deficits by eliminating C1q-tagged synapses in sepsis-associated encephalopathy

40 views | Sep 04 2023

Complement-dependent synaptic pruning by microglia is a key mechanism underlying the development of neuronal damage and cognitive dysfunction in sepsis-associated encephalopathy (SAE). [Read the Full Post]

Phase 1 study of GSK3368715, a type I PRMT inhibitor, in patients with advanced solid tumors

24 views | Sep 03 2023

The Phase 1 study of GSK3368715, a reversible inhibitor of type I protein methyltransferases, was terminated early due to a higher-than-expected incidence of thromboembolic events, limited target engagement at lower doses, and lack of observed clinical efficacy. [Read the Full Post]

Anti-tumor Activity of the Type I PRMT Inhibitor, GSK3368715, Synergizes with PRMT5 Inhibition through MTAP Loss

25 views | Sep 03 2023

GSK3368715, a potent type I PRMT inhibitor, demonstrates anti-tumor effects and its combination with PRMT5 inhibition and consideration of MTAP status as a biomarker strategy show promise for effective oncology treatment. [Read the Full Post]

Targeting cryptic-orthosteric site of PD-L1 for inhibitor identification using structure-guided approach

87 views | Sep 03 2023

This study utilized structure-assisted virtual screening and molecular dynamics simulations to identify two novel small molecule compounds as potential therapeutic candidates for inhibiting the PD-L1 protein-protein interaction in cancer treatment. [Read the Full Post]

Current and emerging pharmacotherapy for the management of hypertrophic cardiomyopathy

77 views | Sep 03 2023

The emerging cardiac myosin inhibitors (CMIs) and ongoing research into targeted therapies and gene therapy hold promise for improving the management and treatment of hypertrophic cardiomyopathy (HCM). [Read the Full Post]

Effect of chronopharmacology and food on in vivo pharmacokinetic profile of mavacamten

87 views | Sep 03 2023

This study found that circadian rhythms significantly impact the pharmacokinetics of mavacamten in rats, while food intake has a minimal effect, highlighting the importance of considering chronopharmacology in optimizing dosing time for this drug. [Read the Full Post]