ATP-¹⁸O₄ disodium

Mitochondria plays an important role in many vital processes in cells, including energy production, fatty-acid oxidation and the Tricarboxylic Acid (TCA) cycle, calcium signaling, permeability transition, apoptosis and heat production. At present, it is recognized that many diseases are associated with impaired mitochondrial function, such as increased accumulation of ROS and decreased OXPHOS and ATP production. Mitochondria are recognized as one of the most important targets for new drug design in cancer, cardiovascular, and neurological diseases, etc. Some small molecule drugs or biologics can act on mitochondria through various pathways, including ETC inhibition, OXPHOS uncoupling, mitochondrial Ca²⁺ modulation, and control of oxidative stress via decrease or increase of mitochondrial ROS accumulation.

MCE supplies a unique collection of 890 mitochondria-targeted compound that mainly targeting Mitochondrial Metabolism, ATP Synthase, Mitophagy, Reactive Oxygen Species, etc. MCE Mitochondria-Targeted Compound Library is a useful tool for mitochondria-targeted drug discovery and related research.

Glycosides are compounds in which a sugar group is bonded through its anomeric carbon to another group via a glycosidic bond. Many biologically active compounds are glycosides. Glycosides comprise several important classes of compounds such as hormones, sweeteners, alkaloids, flavonoids, antibiotics, etc. The glycosidic residue can be crucial for their activity or can only improve pharmacokinetic parameters. Glycosides, which exhibit anti-inflammatory, anti-infection, anti-cancer and anti-oxidative properties, play numerous important roles in living organisms, such as streptomycin, as an aminoglycoside antibiotic, has anti-infection activity. Anthracyclines possess good antibacterial and anti-cancer activities.

MCE Glycoside Compound Library contains a unique collection of 788 glycoside compounds and is a useful tool to discovery glycoside drugs.

Glycolysis is a series of metabolic processes by which one molecule of glucose is catabolized to two molecules of pyruvate with a net gain of two ATP. Glycolysis takes place in 10 steps and catalyzed by a series of enzyme, such as hexokinase, Glucose-6-phosphate isomerase, Phosphofructokinase, etc. Glycolysis is used by all cells in the body for energy generation.

Most cancer cells exhibit increased glycolysis and use this metabolic pathway for generation of ATP as a main source of their energy supply. This phenomenon is known as the Warburg effect and is considered as one of the most fundamental metabolic alterations during malignant transformation. Because increased aerobic glycolysis is commonly seen in a wide spectrum of human cancers, development of novel glycolytic inhibitors as a new class of anticancer agents is likely to have broad therapeutic applications.

MCE provides a unique collection of 689 glycolysis compounds that mainly target hexokinase, glucokinase, enolase, pyruvate kinase, PDHK, etc. MCE Glycolysis Compound Library is a useful tool for glucose metabolism research and anti-cancer drug discovery.

Glutamine is an important metabolic fuel that helps rapidly proliferating cells meet the increased demand for ATP, biosynthetic precursors, and reducing agents. Glutamine Metabolism pathway involves the initial deamination of glutamine by glutaminase(GLS), yielding glutamate and ammonia. Glutamate is converted to the TCA cycle intermediate α-ketoglutarate (α-KG) by either glutamate dehydrogenase (GDH) or by the alanine or aspartate transaminases (TAs), to produce both ATP and anabolic carbons for the synthesis of amino acids, nucleotides and lipids. During periods of hypoxia or mitochondrial dysfunction, α-KG can be converted to citrate in a reductive carboxylation reaction catalyzed by IDH2. The newly formed citrate exits the mitochondria where it is used to synthesize fatty acids and amino acids and produce the reducing agent, NADPH.

Cancer cells display an altered metabolic circuitry that is directly regulated by oncogenic mutations and loss of tumor suppressors. Mounting evidence indicates that altered glutamine metabolism in cancer cells has critical roles in supporting macromolecule biosynthesis, regulating signaling pathways, and maintaining redox homeostasis, all of which contribute to cancer cell proliferation and survival. Thus, intervention in glutamine metabolic processes could provide novel approaches to improve cancer treatment.

MCE owns a unique collection of 903 compounds targeting the mainly proteins and enzymes involved in glutamine metabolism pathway. Glutamine Metabolism compound library is a useful tool for intervention in glutamine metabolic processes.

According to reports, most known kinase inhibitors exert their effects through competitive binding in highly conserved ATP pockets. Although genetic techniques such as RNA interference can inactivate specific genes, most kinases are multi domain proteins, each of which has an independent function. Highly selective inhibitors have higher efficiency than non-selective inhibitors, and the selectivity to the target is at least 100 times higher. Therefore, ensuring the validation of targets with the most selective inhibitors is crucial for a more thorough understanding of the pharmacology of the kinase field. The Highly Selective Inhibitors Library contains 4653 compounds, covering multiple targets and subtypes, such as GPCR protein family, Ion channel, multiple kinases, etc. The Highly Selective Inhibitors Library is an effective tool for screening different phenotypes

Normal mitochondrial function is critical for maintaining cellular homeostasis because mitochondria produce ATP and are the major intracellular source of free radicals. Cellular dysfunctions induced by intracellular or extracellular insults converge on mitochondria and induce a sudden increase in permeability on the inner mitochondrial membrane, the so-called mitochondrial membrane permeability transition (MMPT). MMPT is caused by the opening of pores in the inner mitochondrial membrane, matrix swelling, and outer membrane rupture. The MMPT is an endpoint to initiate cell death because the pore opening together with the release of mitochondrial cytochrome c activates the apoptotic pathway of caspases.

The normal operation of mitochondrial function is important for maintaining normal cell death and treatment of mitochondrial diseases. MCE offers a unique collection of 583 compounds with identified and potential mitochondrial protective activity. MCE Mitochondrial Protection Compound Library is critical for drug discovery and development.

Protein serine/threonine kinases (PSKs) are protein kinases that use ATP as a high-energy donor molecule to transfer phosphate groups to serine/threonine residues of target protein. As an important signal transduction regulator, serine/threonine kinases can affect the function of target proteins by disrupting enzyme activity or binding of target proteins to other proteins. Serine/threonine kinases are involved in the regulation of immune response, cell proliferation, differentiation, apoptosis and other physiological processes. Serine/threonine kinase inhibitors are an important class of compounds that have been widely studied in cancer, chronic inflammation, autoimmune diseases, aging and other diseases.

MCE designs a unique collection of 1267 serine/threonine kinase inhibitors, mainly targeting the receptor PKA, Akt, PKC, MAPK/ERK, etc, which is an effective tool for development and research of anti-cancer, anti-chronic inflammatory diseases, anti-autoimmune diseases and anti-aging compounds.

Most of molecules enter or leave cells mainly via membrane transport proteins, which play important roles in several cellular functions, including cell metabolism, ion homeostasis, signal transduction, the recognition process in the immune system, energy transduction, etc. There are three major types of transport proteins, ATP-powered pumps, channel proteins and transporters. Transport proteins such as channels and transporters play important roles in the maintenance of intracellular homeostasis, and mutations in these transport protein genes have been identified in the pathogenesis of a number of hereditary diseases. In the central nervous system, ion channels have been linked to, but not limited to, many diseases such asataxias, paralyses, epilepsies, and deafness. This indicates the roles of ion channels in the initiation and coordination of movement, sensory perception, and encoding and processing of information. Ion channels are a major class of drug targets in drug development.

MCE designs a unique collection of 1392 smal-molecule modulators that can be used for the research of Ion Channel and Membrane Transporter or high throughput screening (HTS) related drug discovery.

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 2507 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.