T_m value

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 4,971 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.

Fragment-based drug discovery (FBDD) is well suited for discovering both drug leads and chemical probes of protein function; it can cover broad swaths of chemical space and allows the use of creative chemistry. Fragment-based drug discovery is well-established in industry and has resulted in a variety of drugs entering clinical trials, with two, vemurafenib and venetoclax, already approved. FBDD also has key attractions for academia. Notably, it is able to tackle difficult or novel targets for which no chemical matter may be found in existing HTS collections.

MCE designs a unique collection of 22,464 fragment compounds, 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 library is an important source of lead-like drugs.

Macrophages are effector cells of the innate immune system, engulfing bacteria and secreting pro-inflammatory and antibacterial mediators. They are an important component of the first line defense against pathogens and tumor cells. In addition, macrophages play an important role in eliminating damaged cells through programmed cell death. Like all immune cells, macrophages originate from pluripotent hematopoietic stem cells in the bone marrow. Macrophages play key functions in many physiological processes beyond homeostasis and innate immunity, including metabolic function, cell debris clearance, tissue repair, and remodeling. In order to fulfill their different functional roles, macrophages can polarize into a series of phenotypes, including classic (pro inflammatory, M1) and alternative (anti-inflammatory, healing promoting, M2) activation states, as well as a wide range of regulatory phenotypes and subtypes. Macrophages exist in all vertebrate tissues and have a dual function in host protection and tissue damage, maintaining a good balance.

MCE designs a unique collection of 158 macrophage related compounds. It is a good tool to be used for research on Inflammation, cancer 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 748 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.

Immuno-Oncology is a type of immunotherapy that has the specific purpose of treating cancer. It works by stimulating our immune system to fight back. Normally, our immune system is able to destroy cancer cells in our body, however sometimes cancer cells can adapt and mutate, effectively hiding from our immune system. This is when tumors can develop and become a threat to our health. Immuno-oncology involves mobilizing lymphocytes to recognize and eliminate cancer cells using the body’s immune system. There are several immuno-oncology treatments available, including Immune cell therapy (CAR-T), monoclonal antibodies (mABs) and checkpoint inhibitors, cytokines and cancer vaccines.

MCE Small Molecule Immuno-Oncology Compound Library offers 494 bioactive tumor immunology compounds that target some important checkpoints such as PD1/PD-L1, CXCR, Sting, IDO, TLR, etc. This library is a useful tool for Immuno-oncology research.

Extracellular vesicles (EVs) are small membrane binding structures that are released from cells into the surrounding environment and play a crucial role in mediating and regulating intercellular communication related to physiological and pathological processes. EVs are lipid membrane vesicles composed of proteins, lipids, and nucleic acids. EVs can be divided into several types based on their source, such as extracellular vesicles, microcapsules, and apoptotic vesicles. The size range of exosomes is 30-150nm, which are endocrine in multi vesicular endosomes (MVEs); microvesicles (50-1000nm) are secreted directly through extracellular interactions, thereby releasing plasma membrane vesicles. In contrast, apoptotic bodies are usually larger, ranging in size from 1 to 5 μ m. This is generated during programmed cell death. EV plays a crucial role in transmitting information between cells and influencing the behavior and function of receptor cells.

MCE designs a unique collection of 406 small molecules related to extracellular vesicles (EVs). It is a good tool to be used for research on metabolize, cancer and other diseases.

Phenolic compounds are usually referred to as a diverse group of naturally occurring compounds with multiple medical properties, such as antioxidants, antimicrobial properties. Those compounds are commonly found in food and plants. They have high synthetic, medicinal and industrial values. Polyphenols are compounds with multiple phenolic functionalities. Naturally occurring polyphenols are known to have biological activities for use as drugs, for example, in diseases like AIDS, heart ailments, ulcer formation, bacterial infection, mutagenesis and neural disorders.

MCE offers a unique collection of 1,193 natural phenol compounds which is a useful tool for drug discovery as an important source of lead compounds.

Fragment-based drug discovery (FBDD) is well suited for discovering both drug leads and chemical probes of protein function. 3-dimensionality (3D) diversity is pivotal because the molecular shape is one of the most important factors in molecular recognition by a biomolecule. There is a developing appreciation that 3D fragments could offer opportunities that are not provided by 2D fragments.

MCE 3D Diverse Fragment Library consists of 5,196 non-flat fragment-like molecules (average Fsp3 value 0.58). More than 4,700 fragment compounds contain at least one chiral center in the structure. The key concepts that underlie the library design were 3D shape, structural diversity, reactive functionality and fragment-like. This 3D Diverse Fragment Library brings higher fragment hit optimization and increases the likelihood to find innovative hits in FBDD.

Medicine Food Homology (MFH) means that some food themselves are medicines and there is no absolute boundary between them. MFH theory combines the function of food and medicine together scientifically and MFH materials can be used both for food and medicine. Besides nutritional value, MFH materials also have the functions in the prevention and treatment of disease and many other healthcare effects. Food as medicines has many benefits because of their safety while taking drugs will bring inevitable side effect to people. In order to ensure the safe use of functional food, National Health Commission of People's Republic of China made specific provisions on MFH items. More than 100 kinds of widely used MFH materials have been released.

Based on MFH items released by National Health Commission, PRC, MCE carefully designs a unique collection of 1,717 Medicine Food Homology Compounds with high safety that can be used for high throughput and high content screening for drug discovery.