NEWS ｜ 18 October 2024

WIKIMOLE—5-Fluorouracil , Staurosporine , Ruxolitinib

By TargetMol

• 5-Fluorouracil - T0984

5-Fluorouracil (5-FU) is a uracil analog and inhibitor of DNA synthesis, exhibiting antitumor activity by affecting pyrimidine synthesis through thymidylate synthase inhibition; it induces apoptosis and autophagy.

Application:

Research on Drug Resistance

5-Fluorouracil, as an important anticancer drug, has been the focus of various therapeutic developments over the past few decades to enhance its anticancer activity. However, overcoming chemotherapy resistance remains a significant challenge due to factors such as cancer stem cells, cancer relapse, metastasis, and angiogenesis. As a result, research on the mechanisms of 5-Fluorouracil resistance and strategies to improve its therapeutic sensitivity, including resistance reversal, continues to attract substantial attention.

Research on Drug Delivery Systems

One of the most important goals of drug research is to discover and design new materials for formulating 5-Fluorouracil, in order to minimize side effects while maximizing clinical efficacy. Various methods can be used to construct drug carriers.

Research on Combination Therapy

%1-Fluorouracil is a core drug for the treatment of colorectal, gastric, and pancreatic cancers and is often combined with other chemotherapy agents, such as oxaliplatin and irinotecan, to enhance efficacy. Particularly in colorectal cancer, the combination of 5-Fluorouracil with leucovorin has demonstrated significant clinical benefits. Additionally, the sustained delivery of 5-Fluorouracil through thiolated chitosan nanoparticles targeting CD44 has been shown to enhance therapeutic effects in triple-negative breast cancer.

• Staurosporine - T6680

Staurosporine (AM-2282) is a protein kinase inhibitor with ATP-competitive and non-selective inhibitory activity (IC50=6/15/2/3/3000 nM) against PKC, PKA, c-Fgr, phosphorylase kinase and TAOK2. Staurosporine also induces apoptosis.

Application:

Research on Anti-cancer

Staurosporine is a highly potent but non-specific protein kinase inhibitor, particularly targeting tyrosine kinases, and it exhibits strong cytotoxic effects on cancer cells. It is known that morethan 90 types of tyrosine kinases are crucial for malignant transformation and tumor angiogenesis. Tyrosine kinase inhibitors (TKIs) can target both receptor and cytoplasmic kinases, improving cancer prognosis by regulating kinase activation in cancer cells. To investigate the potential mechanisms of apoptosis in cancer cells, Staurosporine is used as an apoptosis inducer in breast cancer cell lines.

Cell Signaling and Cell Cycle Regulation

Staurosporine, as a non-specific protein kinase inhibitor, affects cell signaling and cell cycle regulation by inhibiting the activity of multiple protein kinases. Researchers use Staurosporine as a tool to explore the roles of various protein kinases in processes such as cell growth, differentiation, and apoptosis.

Research on Neuroscience

In the field of neuroscience research, Staurosporine has gained attention for its neuroprotective function. Studies have shown that pentoxifylline has a positive effect on the neurite outgrowth process in PC12 cells induced by Staurosporine. Similarly, at lower concentrations, Staurosporine can promote neurite growth, offering new insights for the treatment of neurodegenerative diseases.

• Ruxolitinib - T1829

Ruxolitinib (INCB018424) is a JAK1/2 inhibitor (IC50=3.3/2.8 nM) that is potent and selective. Rixolitinib exhibits antitumor activity and induces autophagy and apoptosis.

Application:

Hematologic diseases

Ruxolitinib is widely used for the treatment of myelofibrosis and polycythemia vera, as well as other myeloproliferative neoplasms (MPNs). These diseases are characterized by abnormal activation of the JAK-STAT signaling pathway, leading to excessive production of blood cells. Ruxolitinib can effectively alleviate symptoms and improve patients' quality of life. In addition, the JAK-STAT pathway plays a fundamental role in hematologic disorders (MPNs), and treatment with Ruxolitinib can significantly enhance the quality of life for MPN patients.

Autoimmune Disease

Due to its anti-inflammatory properties, Ruxolitinib is also being studied for the treatment of various autoimmune diseases, such as rheumatoid arthritis and psoriasis. A common feature of these diseases is the presence of persistent inflammatory responses in the body. Ruxolitinib can reduce the production of inflammatory mediators by inhibiting the JAK-STAT signaling pathway.

Skin Disease

Ruxolitinib has also shown potential in treating certain skin diseases, such as atopic dermatitis. In these cases, Ruxolitinib can be used topically to reduce skin inflammation and itching.

Tumor Treatment

Although Ruxolitinib was originally developed as a treatment for blood disorders, recent studieshave indicated that it may also be effective for certain types of solid tumors, particularly those that rely on the JAK-STAT pathway.