Blog of Signaling Pathways

A high-throughput screen identifies that CDK7 activates glucose consumption in lung cancer cells

0 views | Apr 03 2023

The study identifies Milciclib as a CDK7 inhibitor that blocks glucose consumption in non-small-cell lung cancer cells with an activated PI3K pathway by decreasing SLC2A1 mRNA and protein levels and inhibiting glucose transport, suggesting that targeting CDK7 may be a promising strategy for developing anti-cancer therapies. [Read the Full Post]

Lipopolysaccharide sensitizes the therapeutic response of breast cancer to IAP antagonist

39 views | Apr 03 2023

The study shows that LPS enhances the therapeutic response of IAP antagonists in treating triple-negative and ER+ breast cancer by inducing rapid apoptosis of cancer cells through TLR4- and MyD88-mediated production of TNFα, and suggests that antibiotics that can reduce microbiota-derived LPS should not be used together with an IAP antagonist for cancer therapy. [Read the Full Post]

Differential roles of phosphatidylinositol 3-kinase/akt pathway in retinal ganglion cell survival in rats with or without acute ocular hypertension

54 views | Apr 03 2023

The study demonstrated that the PI3K/akt pathway is involved in mediating RGC survival following IOP elevation but not under normal conditions, suggesting its potential as a therapeutic target for ocular ischemic injuries and glaucoma. [Read the Full Post]

CUDC907, a dual phosphoinositide-3 kinase/histone deacetylase inhibitor, promotes apoptosis of NF2 Schwannoma cells

55 views | Apr 03 2023

CUDC907, a dual HDAC/PI3K inhibitor, selectively reduces the viability of human merlin deficient Schwann cells (MD-SCs), promotes cell cycle arrest and caspase-3/7 activation, decreases levels of pAKT and YAP, and shows potential as a therapeutic option for Neurofibromatosis Type 2 (NF2). [Read the Full Post]

Co-targeting of HDAC, PI3K, and Bcl-2 results in metabolic and transcriptional reprogramming and decreased mitochondrial function in acute myeloid leukemia

54 views | Apr 03 2023

The study found that the combination of CUDC-907 and venetoclax induces metabolic and transcriptomic reprogramming and suppresses oxidative phosphorylation in AML cells, providing a promising therapeutic approach for AML. [Read the Full Post]

AZ-628 delays osteoarthritis progression via inhibiting the TNF-α-induced chondrocyte necroptosis and regulating osteoclast formation

72 views | Apr 02 2023

AZ-628 has the potential to treat osteoarthritis by inhibiting chondrocyte inflammation and necroptosis, regulating osteoclast formation, and slowing down subchondral bone changes induced by dynamic bone remodeling. [Read the Full Post]

Structure-based mechanism and inhibition of cholesteryl ester transfer protein

36 views | Apr 02 2023

Recent research on cholesteryl ester transfer proteins (CETP) has highlighted their role in regulating plasma cholesterol levels and their potential as a therapeutic target for ASCVD or dyslipidemia, with ongoing research focusing on the structural and mechanistic basis of CETP inhibition to guide the development of more effective anti-ASCVD therapeutics. [Read the Full Post]

ATM-SPARK: A GFP phase separation-based activity reporter of ATM

87 views | Apr 02 2023

ATM-SPARK is a novel method for visualizing and measuring the activity of the kinase ATM during DNA damage response, allowing for the spatiotemporal dynamics of ATM activity to be observed in living cells and enabling high-throughput screening of biological and small-molecule regulators. [Read the Full Post]

A High-Throughput Screening Platform Identifies Novel Combination Treatments for Malignant Peripheral Nerve Sheath Tumors

37 views | Apr 02 2023

The study identified a synergistic combination of MK-1775 with Doxorubicin as a potentially effective pharmacologic option for the treatment of malignant peripheral nerve sheath tumors. [Read the Full Post]

The role of drug efflux and uptake transporters ABCB1 (P-gp), ABCG2 (BCRP) and OATP1A/1B and of CYP3A4 in the pharmacokinetics of the CDK inhibitor milciclib

0 views | Apr 02 2023

The study investigated the impact of transporters and enzymes on the pharmacokinetics of the anticancer drug milciclib, and found that ABCB1 and ABCG2 transporters cooperatively limit milciclib brain penetration, while OATP1 and CYP3A have only a minor impact. [Read the Full Post]

A Novel Quantum Dots-Based Fluorescent Sensor for Determination of the Anticancer Dacomitinib: Application to Dosage Forms

53 views | Apr 01 2023

The study proposes a novel spectrofluorimetric method for determining the concentration of dacomitinib using newly synthesized nitrogen-doped carbon quantum dots as fluorescent probes, which exhibit native fluorescence and are selectively quenched by increasing concentrations of dacomitinib, offering a simple, efficient, and eco-friendly means of determining the concentration of dacomitinib. [Read the Full Post]

An evaluation of fedratinib for adult patients with newly diagnosed and previously treated myelofibrosis

111 views | Apr 01 2023

Fedratinib is a selective JAK2 inhibitor that has been approved by the FDA for the treatment of intermediate-2 or high-risk primary or secondary MF, providing a second-line treatment option for patients who failed or discontinued ruxolitinib, but new combinations with other targeted therapies are needed to improve management of the disease. [Read the Full Post]

Pharmacotherapeutic advances for splenomegaly in myelofibrosis

129 views | Apr 01 2023

Myelofibrosis is a hematologic malignancy characterized by splenomegaly in most patients, with JAK inhibitors being the primary pharmacologic treatment option, but alternative therapies and non-pharmacologic approaches may also be considered, and novel combination therapies are being explored. [Read the Full Post]

Transporter‑mediated drug‑drug interactions involving poly (ADP‑ribose) polymerase inhibitors (Review)

103 views | Apr 01 2023

Transporter-mediated drug-drug interactions should be considered when co-administering PARP inhibitors with other therapeutic agents to avoid potential toxicity or suboptimal efficacy. [Read the Full Post]

CDH6 as a prognostic indicator and marker for chemotherapy in gliomas

52 views | Apr 01 2023

The study suggests that CDH6 may act as a promising target for glioma therapy, based on its positive correlation with tumor grade, negative correlation with patient prognosis, and associations with cell-cell interactions, immune processes, and potential drug targets. [Read the Full Post]

Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent

58 views | Mar 31 2023

The passage describes the pharmacokinetics of geldanamycin in mice and a dog and highlights the potential for acute hepatotoxic reactions, indicating a need for further pharmacological and therapeutic information before considering the drug for clinical development. [Read the Full Post]

Metabolic alterations and mitochondrial dysfunction underlie hepatocellular carcinoma cell death induced by a glycogen metabolic inhibitor

26 views | Mar 31 2023

This study highlights the potential of targeting glycogen metabolism as a therapeutic strategy for HCC through inducing metabolic alterations and mitochondrial dysfunction. [Read the Full Post]

Inhibition of Aurora kinase A activity enhances the antitumor response of beta-catenin blockade in human adrenocortical cancer cells

18 views | Mar 31 2023

Inhibition of Aurora kinases combined with blockade of the Wnt/beta-catenin pathway may provide a promising combinatorial approach for targeting ACC tumors. [Read the Full Post]

Inhibition of p38 signaling curtails the SARS-CoV-2 induced inflammatory response but retains the IFN-dependent antiviral defense of the lung epithelial barrier

30 views | Mar 31 2023

Targeting the p38 MAPK pathway with selective inhibitors could reduce harmful inflammation and improve current treatment strategies for COVID-19, as suggested by recent findings. [Read the Full Post]

New therapies in non-small cell lung cancer with EGFR exon 20 insertion mutations

68 views | Mar 31 2023

The review identified promising therapies for NSCLC with EGFR exon 20 insertion mutations, but further comparative studies with larger sample sizes and better design are needed to confirm their efficacy. [Read the Full Post]