Blog of Signaling Pathways

Cell senescence-associated genes predict the malignant characteristics of glioblastoma

21 views | Dec 03 2023

The study identifies distinct molecular subtypes of glioblastoma based on cell senescence-associated gene expression patterns, develops a robust risk score model associated with patient prognosis and immunotherapy response, and suggests potential therapeutic strategies targeting specific pathways, highlighting the importance of personalized medicine in GBM treatment. [Read the Full Post]

Tight junction and kidney stone disease

18 views | Dec 03 2023

The review discusses the involvement of tight junction defects in kidney stone disease, emphasizing the disruption of renal tubular epithelial cell tight junctions by calcium oxalate crystals and genetic factors, and explores potential therapeutic strategies targeting tight junction function. [Read the Full Post]

ALKBH5 causes retinal pigment epithelium anomalies and choroidal neovascularization in age-related macular degeneration via the AKT/mTOR pathway

19 views | Dec 02 2023

ALKBH5 upregulation in age-related macular degeneration leads to retinal pigment epithelium dysfunction and choroidal neovascularization through its demethylation activity, activating the PIK3C2B-mediated AKT/mTOR pathway, and pharmacological inhibitors like IOX1 offer potential therapeutic interventions. [Read the Full Post]

Discovery of 4-(((4-(5-chloro-2-(((1s,4s)-4-((2-methoxyethyl)amino)cyclohexyl)amino)pyridin-4-yl)thiazol-2-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile (JSH-150) as a novel highly selective and potent CDK9 kinase inhibitor

16 views | Dec 02 2023

Compound 40 (JSH-150) is a highly selective CDK9 kinase inhibitor with an IC50 of 1 nM, demonstrating potent antiproliferative effects across multiple cancer cell lines, robust in vivo efficacy, and a promising pharmacological tool and drug candidate for leukemia and other cancers. [Read the Full Post]

Optimization of a Glucagon-Like Peptide 1 Receptor Antagonist Antibody for Treatment of Hyperinsulinism

19 views | Dec 02 2023

A highly potent GLP-1R antagonist antibody, TB-222-023, derived from a combinatorial variant antibody library, effectively decreases insulin secretion in hyperinsulinism mouse models and human islets, offering a promising therapeutic strategy for congenital hyperinsulinism. [Read the Full Post]

Targeting SWI/SNF ATPases in H3.3K27M diffuse intrinsic pontine gliomas

17 views | Dec 02 2023

H3K27M mutations in diffuse midline gliomas reprogram the SWI/SNF complex, leading to upregulated SMARCA4 levels, and therapeutic targeting of SMARCA4, SMARCA2, and PBRM1 using AU-15330 selectively induces cytotoxicity in H3.3K27M-mutant cells, suggesting a potent and specific therapeutic strategy for these deadly childhood brain tumors. [Read the Full Post]

Cuminum cyminum Ameliorates Urotoxic Effects of Cyclophosphamide by Modulating Antioxidant, Inflammatory Cytokines, and Urinary Bladder Overactivity: In vivo and In Silioc investigations

20 views | Dec 02 2023

The study demonstrates that the aqueous ethanol extract of Cuminum cyminum attenuates cyclophosphamide-induced bladder toxicity in rats by reducing oxidative stress, inflammation, and smooth muscle overactivity, while in silico analysis identifies potential bioactive compounds for future drug development. [Read the Full Post]

Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells

35 views | Dec 01 2023

The study elucidates the role of NUDT5 in ADP-ribose metabolism and hormone-dependent gene regulation in breast cancer cells, presenting TH5427 as a potent inhibitor that blocks nuclear ATP synthesis, chromatin remodeling, and proliferation, highlighting its potential for targeted therapy and further research. [Read the Full Post]

NR4A1 as a potential therapeutic target in colon adenocarcinoma: a computational analysis of immune infiltration and drug response

18 views | Dec 01 2023

Targeting NR4A1 with OSI-930 may offer a promising therapeutic strategy for colon adenocarcinoma patients with high immune infiltration, pending rigorous clinical validation. [Read the Full Post]

Preclinical Efficacy of Covalent-Allosteric AKT Inhibitor Borussertib in Combination with Trametinib in KRAS-Mutant Pancreatic and Colorectal Cancer

23 views | Dec 01 2023

The discovery of borussertib, a covalent-allosteric AKT inhibitor, and its demonstrated efficacy in combination with the MEK inhibitor trametinib in patient-derived xenograft models represent a promising advancement in targeted cancer therapy for individuals with specific genetic alterations in the PTEN, PI3K, and RAS signaling pathways. [Read the Full Post]

Identification of potential RapJ hits as sporulation pathway inducer candidates in Bacillus coagulans via structure-based virtual screening and molecular dynamics simulation studies

56 views | Dec 01 2023

Computational analyses identified acarbose as a potential inhibitor of the RapJ enzyme, crucial for inducing the sporulation pathway in Bacillus coagulans, but experimental validation is necessary to confirm its effectiveness. [Read the Full Post]

Antifibrotic mechanism of avitinib in bleomycin-induced pulmonary fibrosis in mice

22 views | Dec 01 2023

A new study demonstrates that avitinib attenuates bleomycin-induced pulmonary fibrosis in mice by inhibiting alveolar epithelial cell injury and myofibroblast activation, indicating its potential as a therapeutic option for this condition. [Read the Full Post]

HDAC3 inhibitor (BRD3308) modulates microglial pyroptosis and neuroinflammation through PPARγ/NLRP3/GSDMD to improve neurological function after intraventricular hemorrhage in mice

47 views | Dec 01 2023

BRD3308 (BRD), an inhibitor of histone deacetylase 3 (HDAC3), reduces neuroinflammation, inhibits pyroptosis, and improves neurobehavioral outcomes in a mouse model of intraventricular hemorrhage by activating the PPARγ/NLRP3/GSDMD signaling pathway. [Read the Full Post]

Low WIP1 Expression Accelerates Ovarian Aging by Promoting Follicular Atresia and Primordial Follicle Activation

27 views | Nov 30 2023

Decreased wild-type P53-induced phosphatase 1 (WIP1) expression accelerates ovarian aging by promoting excessive follicular atresia, primordial follicle activation, and granulosa cell death, leading to irregular estrous cycles, fertility decline, and reduced ovarian reserve in mice. [Read the Full Post]

Inverse Impact of Cancer Drugs on Circular and Linear RNAs in Breast Cancer Cell Lines

36 views | Nov 30 2023

The study investigated the dysregulation of cancer-related circular RNAs (circRNAs) and their linear transcripts (linRNAs) in breast cancer cell lines exposed to various anticancer drugs, revealing altered circRNA/linRNA expression ratios and identifying specific circRNAs associated with apoptosis, cell migration, and mutated pathways, thereby shedding light on their potential roles as biomarkers and therapeutic targets in breast cancer treatment. [Read the Full Post]

Regional regulatory harmonisation initiatives: Their potential contribution to the newly established African medicines agency

82 views | Nov 30 2023

The study highlights the foundational role of regional medicines regulatory harmonization programs, such as the African Medicines Regulatory Harmonisation (AMRH) and East African Community Medicines Regulatory Harmonisation (EAC-MRH) initiatives, in supporting the operationalization of the African Medicine Agency (AMA), emphasizing the importance of strong national regulatory authorities and increased ratification of the AMA Treaty for ensuring access to essential medical products and technologies for the African people. [Read the Full Post]

The anticonvulsant effect of saiga horn on febrile seizures by regulating brain serotonin content and inhibiting neuroinflammation

67 views | Nov 30 2023

Saiga antelope horn (SAH) demonstrates significant anticonvulsant effects in a febrile seizures rat model by modulating neurotransmitter levels, exerting anti-inflammatory actions, and activating the ER-β/TPH2/5-HT signaling pathway, offering potential insights for the development of SAH-based treatments and substitutes. [Read the Full Post]

Finding Lead Compounds for Dengue Antivirals from a Collection of Old Drugs through In Silico Target Prediction and Subsequent In Vitro Validation

33 views | Nov 30 2023

This study utilized ligand-based and proteochemometric prediction models, coupled with experimental assays and molecular docking, to identify and validate potential DENV NS3 inhibitors, highlighting five promising lead compounds (ziltri, zilool, zileuton, linalool, and trimethadione) for further development as antiviral treatments. [Read the Full Post]

Lauric Acid, a Dietary Saturated Medium-Chain Fatty Acid, Elicits Calcium-Dependent Eryptosis

35 views | Nov 29 2023

The study demonstrates that lauric acid induces eryptosis, a programmed cell death in red blood cells, and disrupts leukocyte distribution, providing key insights into its role in cardiovascular diseases and informing dietary interventions for prevention and management. [Read the Full Post]

TRUST-II: a global phase II study of taletrectinib in ROS1-positive non-small-cell lung cancer and other solid tumors

23 views | Nov 29 2023

TRUST-II is a global phase II study evaluating taletrectinib's efficacy and safety in treating ROS1+ non-small-cell lung cancer and other ROS1+ solid tumors, with confirmed objective response rate as the primary endpoint and secondary endpoints including duration of response, progression-free survival, overall survival, and safety assessments, enrolling patients across North America, Europe, and Asia to address unmet needs in overcoming resistance, treating brain metastasis, and reducing neurological side effects. [Read the Full Post]