Pi

The PI3K/Akt/mTOR pathway controls many cellular processes that are important for the formation and progression of cancer, including apoptosis, transcription, translation, metabolism, angiogenesis, and cell cycle progression. Every major node of this signaling network is activated in a wide range of human tumors. Mechanisms for the pathway activation include activation of receptor tyrosine kinases (RTKs) upstream of PI3K, mutation or amplification of PIK3CA encoding p110α catalytic subunit of PI3K, mutation or loss of PTEN tumor suppressor gene, and mutation or amplification of Akt1. Once the pathway is activated, signaling through Akt can stimulate a series of substrates including mTOR which is involved in protein synthesis. Thus, inhibition of this pathway is an attractive concept for cancer prevention and/or therapy. Currently some mTOR inhibitors are approved for several indications, and there are several novel PI3K/Akt/mTOR inhibitors in clinical trials.

MCE owns a unique collection of 808 compounds that can be used for PI3K/Akt/mTOR pathway research. PI3K/Akt/mTOR Compound Library also acts as a useful tool for anti-cancer drug discovery.

Kinase is an enzyme that adds phosphate groups to other molecules. This process is known as phosphorylation. Protein phosphorylation is a key aspect in the regulation of a large number of cellular processes including cellular division, metabolism, signal transduction, and so on. There are over 500 kinases encoded by the human genome and it has been estimated that kinases regulate approximately 50% of cellular functions. Kinases are a large group of drug targets in drug discovery. Kinase inhibitors are an important class of drugs that block certain enzymes involved in diseases such as cancer and inflammatory disorders.

Kinase inhibitor library designed by MCE contains 3,287 kinase inhibitors and regulators mainly targeting protein kinases (VEGFR, EGFR, BTK, CDK, Akt, etc.), lipid kinases (PI3K, PI4K, SK, etc.) and carbohydrate kinases (Hexokinase), and is a useful tool for kinase drug discovery and related research.

Fibrosis is a kind of repair response to long-term tissue damage, which is mainly manifested by excessive deposition of extracellular matrix (ECM) and scar formation. Myofibroblasts are the main generating cells of extracellular matrix, and their activation process is related to various pathological mechanisms including Oxidative stress, chronic inflammation and cytokine secretion. Fibrosis can occur in many organs, such as kidneys, liver, heart, lungs, etc. Continuous fibrosis can lead to the destruction of the normal structure of tissues and organs, and if not controlled in time, may cause organ failure or even life-threatening.

MCE contains 1,980 compounds targeting ant-fibrosis targets such as TGF-β, PI3K, Wnt, MMP, etc. These compounds have clear or potential anti-fibrosis activity and can be used for mechanism research and drug screening of fibrosis diseases.

Oxygen homeostasis regulation is the most fundamental cellular process for adjusting physiological oxygen variations, and its irregularity leads to various human diseases, including cancer. Hypoxia is closely associated with cancer development, and hypoxia/oxygen-sensing signaling plays critical roles in the modulation of cancer progression.

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis. A variety of HF-1 target genes have been identified thus far which encode proteins that play key roles in critical developmental and physiological processes including angiogenesis/vascular remodeling, erythropoiesis, glucose transport, glycolysis, iron transport, and cell proliferation/survival.

HIF-1 is a heterodimeric transcription factor consisting of a constitutively expressed β-subunit and an oxygen-regulated α-subunit. The unique feature of HIF-1 is the regulation of HIF-1α expression and activity based upon the cellular O₂ concentration. Under normoxic conditions, hydroxylation of HIF-1α on these different proline residues is essential for HIF proteolytic degradation by promoting interaction with the von Hippel-Lindau tumor-suppressor protein (pVHL) through hydrogen bonding to the hydroxyproline-binding pocket in the pVHL β-domain. As oxygen levels decrease, hydroxylation of HIF decreases; HIF-1α then no longer binds pVHL, and becomes stabilized, allowing more of the protein to translocate to the cell’s nucleus, where it acts as a transcription factor, upregulating (often within minutes) the production of proteins that stimulate blood perfusion in tissues and thus tissue oxygenation.

MCE offers a unique collection of 3,221 oxygen sensing related compounds targeting HIF/HIF Prolyl-Hydroxylase, MAPK/ERK, PI3K/AKT signaling pathways, etc. MCE Oxygen Sensing Compound Library is a useful tool to study hypoxia, oxidative stress and discover new anti-cancer drugs.

Pulmonary fibrosis (PF), also known as diffuse interstitial pulmonary fibrosis, is a very common end-stage manifestation of several diseases, including idiopathic pulmonary fibrosis (IPF), pulmonary hypertension, and scleroderma, characterised by excessive matrix deposition and destruction of the lung architecture, finally leading to respiratory insufficiency. PF has become a global disease with significantly increased incidence rate, and the most common form of pulmonary fibrosis is idiopathic pulmonary fibrosis (IPF).

Lung fibrosis is a complex disease, a multitude of signal factors and signaling pathways is disrupted in this complex disease, such as TGF-β, Wnt, VEGF and PI3K–Akt. MCE offers a unique collection of 2,182 compounds with identified and potential anti-pulmonary fibrosis activity. MCE Anti-Pulmonary Fibrosis Compound Library is a useful tool for anti-pulmonary fibrosis drugs screening and other related research.

Liver cancer is one of the leading malignancies which occupies the second position in cancer deaths worldwide, becoming serious threat to human health. Hepatocellular carcinoma (HCC), also known as hepatoma is the most common type accounting for approximately 90% of all liver cancers.

Current evidence indicates that during hepatocarcinogenesis, two main pathogenic mechanisms prevail: (1) cirrhosis associated with hepatic regeneration after tissue damage caused by hepatitis infection, toxins or metabolic influences, and (2) mutations occurring in single or multiple oncogenes or tumor suppressor genes. Both mechanisms have been linked with alterations in several important cellular signaling pathways. These include the RAF/MEK/ERK pathway, PI3K/AKT/mTOR pathway, WNT/b-catenin pathway, insulin-like growth factor pathway, c-MET/HGFR pathway , etc.

MCE offers a unique collection of 2,362 compounds with identified and potential anti-liver cancer activity. MCE anti-liver cancer compound library is a useful tool for anti-liver cancer drugs screening and other related research.

Breast cancer is the most frequent cancer among women, impacting 2.1 million women each year, and also causes the greatest number of cancer-related deaths among women. Surgery is usually the first type of treatment for breast cancer, which is usually followed by chemotherapy or radiotherapy or, in some cases, hormone or targeted therapies, especially for metastatic breast cancer (MBC).

Breast cancer is a heterogeneous disease, which is categorized into 3 major subtypes based on the presence or absence of molecular markers for estrogen or progesterone receptors and human epidermal growth factor 2 (ERBB2; formerly HER2): hormone receptor positive/ERBB2 negative (70% of patients), ERBB2 positive (15%-20%), and triple-negative (tumors lacking all 3 standard molecular markers; 15%). Different intrinsic subtypes exhibit different tumor behavior with different prognoses, and may require specific targeted therapies to maximize treatment effectiveness. Otherwise, some signaling pathways also play important roles in the development of breast cancer, such as NF-κB Signaling Pathway, TGF-beta Signaling Pathway, PI3K/AKT/mTOR signaling pathway and Notch Signaling Pathway. These signaling pathways offer ideal targets for development of new targeted therapies for breast cancer.

MCE supplies a unique collection of 2,589 compounds with identified and potential anti-breast cancer activity. MCE Anti-Breast Cancer Compound Library is a useful tool for anti-breast cancer drugs screening.

Neurodegenerative diseases are characterised by progressive dysfunction and death of neurons, such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis (MS). Neuroprotection is an approach to preserve neurons so that neurons cannot be hurt by different pathological factors in neurodegenerative diseases. Neuroprotectors are some agonists and antagonists targeting some key targets in neuroprotactive signal pathways, such as calcium and sodium channel blockers, GABA receptor agonists, NMDA receptor Antagonists, etc. Current neuroprotectors cannot reverse existing damage, but they may protect against further nerve damage and slow down any degeneration of the central nervous system (CNS) and still play important roles in the treatment of neurodegenerative diseases.

MCE offers a unique collection of 1,436 compounds with potential neuroprotective activities. These compounds mainly act on some key targets in neuroprotetive signal pathways, such as calcium channel, sodium channel, adenosine A1 receptor, etc. MCE Neuroprotective Compopund Library is a useful tool in neuroprotective drug discovery.

Pancreatic cancer is a devastating disease with a low overall survival rate. Chemotherapy is the most common treatment for patients presenting with advanced pancreatic cancer. More recently, the era of targeted therapies has generated a lot of interest in discovering better approaches for patients with pancreatic cancer. Commonly mutated genes in pancreatic cancer include K-ras (in 74-100% of cases), p16INK4a (up to 98%), p53 (43 to 76%), DPC4 (about 50%), HER-2/neu (in about 65%) and FHIT (found in 70% of cases). Other genes involved are notch1, Akt-2, BRCA2 and COX-2. These proteins are important targets of target therapies for pancreatic cancer.

MCE offers a unique collection of 3,403 compounds with identified and potential anti- pancreatic cancer activity. These compounds target K-Ras, p53, HER2, Notch, AKT, etc. MCE anti-pancreatic cancer compound library is a useful tool for anti-pancreatic cancer drugs screening and other related research.

Blood cancers, also called hematologic cancers, occur when abnormal blood cells start growing out of control, interrupting the function of normal blood cells, which fight off infection and produce new blood cells. Most blood cancers start in the bone marrow, which is where blood is produced. There are three main types of blood cancers: leukemia, lymphoma and myeloma, which afflict millions of children and adults every year, and are often deadly.

Some common blood cancer treatments include stem cell transplantation, chemotherapy, radiation therapy, targeted therapy, immunotherapy or a combination thereof. As we begin to understand the key signaling pathways and molecular drivers of malignant transformation in haematological disorders, new treatment strategies will continue to be developed.

MCE offers a unique collection of 3,424 compounds with identified and potential anti-blood cancer activity. These compounds target blood cancer’s major targets and signaling pathways. MCE anti-blood cancer compound library is a useful tool for anti-blood cancer drugs screening and other related research.

Recently, significant advancements in tyrosine-targeting electrophiles have primarily occurred in the field of protein-protein interactions (PPIs), where cysteine residues are often underrepresented and novel chemistries are needed to address these interfaces. In this context, tyrosines are frequently more accessible compared to more buried binding sites. Moreover, they are commonly found at "hot spots," which are functional epitopes of PPIs, with 12.3% of the residues consisting of tyrosines. This prevalence is likely due to the hydrophobic nature of tyrosine, its ability to participate in aromatic π-interactions, and its capacity for hydrogen bonding. Beyond PPIs, some progress has also been made in covalent tyrosine targeting in other areas where more commonly addressed side chains are lacking. Even though tyrosine has a slightly lower pKa value compared to the protonated lysine side chain (approximately 10 vs. 10.5 for the unprotected amino acid side chains), significantly less progress has been made in the development of tyrosine-targeted covalent ligands compared to lysine. This is likely due to the reduced flexibility of the tyrosine side chain and the greater steric hindrance of its hydroxy group, which makes it more challenging to adopt suitable reaction geometries.

Through careful selection, we constructed a structural filter containing over 110 electrophilic groups. By analyzing the electrophilic fragments selected by the structural filter, we removed any molecules with trivial or undesirable structural features. Ultimately, we obtained 124 fragment molecules which can target tyrosine residue and can be used for fragment-based covalent drug discovery.

MCE Cell Cycle and Apoptosis Analysis Kit (PI staining) provides a convenient method to detect cell cycle and cell apoptosis.

MCE YO-PRO-1/PI Apoptosis and Necrosis Detection Kit is a dual-fluorescence method based on the green fluorescent dye YO-PRO-1 (YP1) and the red fluorescent dye Propidium Iodide (PI) for detecting cell apoptosis and necrosis.

MCE Annexin V-iFluor 488/PI Apoptosis Detection Kit provides a rapid and convenient method to detect cell apoptosis and necrosis. After staining, live cells show little or no fluorescence (Annexin V-/PI-),, early apoptosis cells show green fluorescence (Annexin V+/PI-), late apoptosis cells and necrosis cells show red and green fluorescence (Annexin V+/PI+).

MCE Annexin V-FITC/PI Apoptosis Detection Kit provides a rapid and convenient method to detect cell apoptosis and necrosis. After staining, live cells show little or no fluorescence (Annexin V-/PI-), early apoptosis cells show green fluorescence(Annexin V+/PI-), late apoptosis cells and necrosis cells show red and green fluorescence (Annexin V+/PI+).

MCE VF 647A-Annexin V/PI Apoptosis Detection Kit can be utilized to detect the level of cell apoptosis.

MCE Viability/Cytotoxicity Assay Kit for Live & Dead Cells (Calcein/PI) enables dual fluorescent staining of both live and dead cells, making it suitable for assessing cell viability and cytotoxicity.

Annexin V-EGFP/PI Apoptosis Detection Kit provides a rapid and convenient method to detect cell apoptosis and necrosis. After staining, live cells show little or no fluorescence (Annexin V-/PI-), early apoptosis cells show green fluorescence(Annexin V+/PI-), late apoptosis cells and necrosis cells show red and green fluorescence (Annexin V+/PI+). Compared with FITC, the fluorescence of EGFP is stronger and more stable.