Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature mainly by processes of sprouting and splitting, but processes such as coalescent angiogenesis, vessel elongation and vessel cooption also play a role. Vasculogenesis is the embryonic formation of endothelial cells from mesoderm cell precursors, and from neovascularization, although discussions are not always precise. The first vessels in the developing embryo form through vasculogenesis, after which angiogenesis is responsible for most, if not all, blood vessel growth during development and in disease.
Batrachotoxin (BTX) is an extremely potent cardio- and neurotoxic steroidal alkaloid found in certain species of beetles, birds, and frogs. The name is from the Greek word βάτραχος, bátrachos, 'frog'. Structurally-related chemical compounds are often referred to collectively as batrachotoxins. In certain frogs, this alkaloid is present mostly on the skin. Such frogs are among those used for poisoning darts. Batrachotoxin binds to and irreversibly opens the sodium channels of nerve cells and prevents them from closing, resulting in paralysis and death. No antidote is known.
Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase that mediates the addition of phosphate molecules onto serine and threonine amino acid residues. First discovered in 1980 as a regulatory kinase for its namesake, glycogen synthase (GS), GSK-3 has since been identified as a protein kinase for over 100 different proteins in a variety of different pathways. In mammals, including humans, GSK-3 exists in two isozymes encoded by two homologous genes GSK-3α (GSK3A) and GSK-3β (GSK3B). GSK-3 has been the subject of much research since it has been implicated in a number of diseases, including type 2 diabetes, Alzheimer's disease, inflammation, cancer, addiction and bipolar disorder.
Tropinone is an alkaloid, famously synthesised in 1917 by Robert Robinson as a synthetic precursor to atropine, a scarce commodity during World War I. Tropinone and the alkaloids cocaine and atropine all share the same tropane core structure. Its corresponding conjugate acid at pH 7.3 major species is known as tropiniumone.
Vascular endothelial growth factor, originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, the platelet-derived growth factor family of cystine-knot growth factors. They are important signaling proteins involved in both vasculogenesis and angiogenesis.
An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels (angiogenesis). Some angiogenesis inhibitors are endogenous and a normal part of the body's control and others are obtained exogenously through pharmaceutical drugs or diet.
Angiogenin (ANG) also known as ribonuclease 5 is a small 123 amino acid protein that in humans is encoded by the ANG gene. Angiogenin is a potent stimulator of new blood vessels through the process of angiogenesis. Ang hydrolyzes cellular RNA, resulting in modulated levels of protein synthesis and interacts with DNA causing a promoter-like increase in the expression of rRNA. Ang is associated with cancer and neurological disease through angiogenesis and through activating gene expression that suppresses apoptosis.
Chelerythrine is a benzophenanthridine alkaloid present in the plant Chelidonium majus. It is a potent, selective, and cell-permeable protein kinase C inhibitor in vitro. And an efficacious antagonist of G-protein-coupled CB1 receptors. This molecule also exhibits anticancer qualities and it has served as a base for many potential novel drugs against cancer. Structurally, this molecule has two distinct conformations, one being a positively charged iminium form, and the other being an uncharged form, a pseudo-base.
Mitogen-activated protein kinase 7 also known as MAP kinase 7 is an enzyme that in humans is encoded by the MAPK7 gene.
Cell division protein kinase 8 is an enzyme that in humans is encoded by the CDK8 gene.
Thiostrepton is a natural cyclic oligopeptide antibiotic of the thiopeptide class, derived from several strains of streptomycetes, such as Streptomyces azureus and Streptomyces laurentii. Thiostrepton is a natural product of the ribosomally synthesized and post-translationally modified peptide (RiPP) class.
Fasudil (INN) is a potent Rho-kinase inhibitor and vasodilator. Since it was discovered, it has been used for the treatment of cerebral vasospasm, which is often due to subarachnoid hemorrhage, as well as to improve the cognitive decline seen in stroke patients. It has been found to be effective for the treatment of pulmonary hypertension. It has been demonstrated that fasudil could improve memory in normal mice, identifying the drug as a possible treatment for age-related or neurodegenerative memory loss.
Angiogenesis is the process of forming new blood vessels from existing blood vessels, formed in vasculogenesis. It is a highly complex process involving extensive interplay between cells, soluble factors, and the extracellular matrix (ECM). Angiogenesis is critical during normal physiological development, but it also occurs in adults during inflammation, wound healing, ischemia, and in pathological conditions such as rheumatoid arthritis, hemangioma, and tumor growth. Proteolysis has been indicated as one of the first and most sustained activities involved in the formation of new blood vessels. Numerous proteases including matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase domain (ADAM), a disintegrin and metalloproteinase domain with throbospondin motifs (ADAMTS), and cysteine and serine proteases are involved in angiogenesis. This article focuses on the important and diverse roles that these proteases play in the regulation of angiogenesis.
Crenolanib besylate is an investigational inhibitor being developed by AROG Pharmaceuticals, LLC. The compound is currently being evaluated for safety and efficacy in clinical trials for various types of cancer, including acute myeloid leukemia (AML), gastrointestinal stromal tumor (GIST), and glioma. Crenolanib is an orally bioavailable benzimidazole that selectively and potently inhibits signaling of wild-type and mutant isoforms of class III receptor tyrosine kinases (RTK) FLT3, PDGFR α, and PDGFR β. Unlike most RTK inhibitors, crenolanib is a type I mutant-specific inhibitor that preferentially binds to phosphorylated active kinases with the ‘DFG in’ conformation motif.
Volasertib is an experimental small molecule inhibitor of the PLK1 protein being developed by Boehringer Ingelheim for use as an anti-cancer agent. Volasertib is the second in a novel class of drugs called dihydropteridinone derivatives.
Balanol is a fungal metabolite produced by the fungus Verticillium balanoides. It is a potent inhibitor of the serine/threonine kinases protein kinase A (PKA) and protein kinase C (PKC), binding in a similar manner with that of ATP. Balanol was discovered in 1993 in the search for novel inhibitors of PKC, a member of a family of serine/threonine kinases whose overactivation is associated with numerous human diseases of signal transduction including cancer. However, much of the research on balanol focuses on how chemical modifications of the molecular structure affect binding to PKA. Indeed, balanol, its chemically altered analogs, and their interactions with PKA in particular are used to illuminate the roles of selectivity and protein flexibility in the inhibition of kinases. For instance, the X-ray crystal structure of balanol in complex with PKA was used in order to confer selectivity and to improve pharmacological efficacy of inhibitors of the H. sapiens Akt (PKB), another serine/threonine protein kinase implicated in the proper functioning of many cellular processes.
4-Nonylphenylboronic acid is a potent and selective inhibitor of the enzyme fatty acid amide hydrolase (FAAH), with an IC50 of 9.1nM, and 870x selectivity for FAAH over the related enzyme MAGL, which it inhibits with an IC50 of 7900nM. It is also a weaker inhibitor of the enzymes endothelial lipase and lipoprotein lipase, with IC50 values of 100 nM and 1400 nM respectively.
Immunomodulatory imide drugs (IMiDs) are a class of immunomodulatory drugs containing an imide group. The IMiD class includes thalidomide and its analogues. These drugs may also be referred to as 'Cereblon modulators'. Cereblon (CRBN) is the protein targeted by this class of drugs.
VEGFR-2 inhibitor, also known as kinase insert domain receptor(KDR) inhibitor, are tyrosine kinase receptor inhibitors that reduce angiogenesis or lymphangiogenesis, leading to anticancer activity. Generally they are small, synthesised molecules that bind competitively to the ATP-site of the tyrosine kinase domain. VEGFR-2 selective inhibitor can interrupt multiple signaling pathways involved in tumor, including proliferation, metastasis and angiogenesis.
2-Methoxyethoxymethyl chloride is an organic compound with formula CH3OCH2CH2OCH2Cl. A colorless liquid, it is classified as a chloroalkyl ether. It is used as an alkylating agent. In organic synthesis, it is used for introducing the methoxyethoxy ether (MEM) protecting group. MEM protecting groups are generally preferred to methoxymethyl (MOM) protecting groups, both in terms of formation and removal.
