drug sensitivity

19F-NMR has proved to be a detection mode in fragment-based drug discovery (FBDD) for studies of protein structure and interactions. 19F shows high sensitivity for NMR detection, and the exquisite sensitivity of 19F chemical shifts and linewidths to ligand binding all make it a valuable approach in FBDD.F (Fluorine) -Fragments can be used for 19F-NMR detection after binding to target proteins, and can be used as an effective 19F-NMR tool for FBDD.

MCE designs a unique collection of 5,123 F-fragments, all of which obey a heuristic rule called the “Rule of Three (RO3)”, in which molecular weight ≤300 Da, the number of hydrogen bond donors (H-donors) ≤3, the number of hydrogen bond acceptors (H-acceptors) is ≤3 and cLogP is ≤3. This F-fragments library is an important source of lead-like drugs.

Radiation sickness is a general term for various types and degrees of damage (or disease) occurring in the human body after exposure to ionizing radiation. Although small amounts of ionizing radiation can also cause the body to produce free radicals and ROS, causing oxidative stress, resulting in DNA damage and chromosomal aberration. Radioprotector are compounds with radiation protection that can be used to prevent/protect non-tumor cells from the harmful effects of radiation. Radioprotective compounds can prevent the damage of radioactive substances to the human body and reduce the clinical symptoms of various radioactive diseases. In addition, radioprotectors can protect normal cells from damage during radiation therapy. The ideal anti-radiation drug should not affect the sensitivity of tumor cells to radiation therapy while protecting normal cells.

MCE designs a unique collection of 2,846 radioprotectors. Radioprotector Library is an effective tool for acute Radiation Syndrome, drug combination research with radiation drugs.

Radiotherapy is a common treatment for various cancers, and more than 50% of cancer patients require radiotherapy during the disease treatment. With advances in radiation technology and a better understanding of tumor biology, the efficacy of radiation therapy has gradually improved, and more and more patients have benefited from it. However, even with the use of advanced radiotherapy techniques, there are still many malignant tumor cells with low sensitivity to radiation, leading to the radiation effect is not ideal. To solve this problem, radiosensitizers have received more and more attention. Radiosensitizer is a kind of drug that can enhance the radiosensitivity of tumor cells and improve the effect of radiotherapy. Radiation sensitizers act in a variety of ways, such as killing hypoxic cells, enhancing DNA damage, inhibiting DNA damage repair, and blocking cell cycle progression, making tumor cells more susceptible to radiation damage and death than surrounding normal cells.

MCE designs a unique collection of 41 compounds with definite reported radiosensitization. It can be used for drug combination research in anti-cancer treatment.

Lipids are important energy storage substances in the human body. They are involved in the regulation of cell structure and function, as well as signaling pathways and gene expression. Abnormal lipid levels in tissues or their dysregulation can lead to various diseases. These include obesity, type 2 diabetes, non-alcoholic fatty liver disease, neurodegenerative diseases, infections, and cancer. Therefore, maintaining normal levels of lipid metabolism is critical to overall health.

One of the key features of cancer is aberrant lipid metabolism. This includes alterations in lipid uptake, lipid desaturation, neolipogenesis, lipid droplets, and fatty acid oxidation in cancer cells. These changes all contribute to cellular survival in an ever-changing microenvironment. They do this by modulating feed-forward oncogenic signals and key oncogenic functions. Additionally, they affect oxidative stress, other types of stress, immune responses, and intercellular communication. Alterations in lipid metabolism have a strong impact on the properties of cancer stem cells. This includes aspects such as self-renewal, differentiation, invasion, metastasis, drug sensitivity, and resistance. Furthermore, these alterations also modulate T cell responses.

MCE can offer 145 metabolites of lipid metabolism pathways, which can be used for drug screening in cancer, immune-based diseases, metabolic diseases, and other diseases.

Diabetes mellitus, usually called diabetes, is a group of metabolic disorders characterized by a high blood sugar level over a prolonged period of time. The most common types are Type I and Type II. Type I diabetes (T1D), also called juvenile onset diabetes mellitus or insulin-dependent diabetes mellitus, is characterized by destruction of the β-cells of the pancreas and insulin is not produced, whereas type II diabetes (T2D), also called non-insulin-dependent diabetes mellitus, is characterized by a progressive impairment of insulin secretion and relative decreased sensitivity of target tissues to the action of this hormone. Type 2 diabetes accounts for the vast majority of all diabetes mellitus. Diabetes of all types can lead to complications in many parts of the body and can increase the overall risk of dying prematurely. Possible complications include kidney failure, leg amputation, vision loss and nerve damage.

The pathogenesis of diabetes is complicated, and development of the safe and effective drugs against diabetes is full of challenge. Increasing studies have confirmed that the pathogenesis of diabetes is related to various signaling pathways, such as insulin signaling pathway, AMPK pathway, PPAR regulation and chromatin modification pathways. These signaling pathways have thus become the major source of the promising novel drug targets to treat metabolic diseases and diabetes.

MCE Anti-diabetic Compound Library owns a unique collection of 1,113 compounds, which mainly target SGLT, PPAR, DPP-4, AMPK, Dipeptidyl Peptidase, Glucagon Receptor, etc. This library is a useful tool for discovery anti-diabetes drugs.