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Sulanemadlin
Sulanemadlin (development code ALRN-6924) is an experimental drug for the treatment of cancer. It is under development by Aileron Therapeutics, and has been studied in clinical trials for myelodysplastic syndrome and acute myeloid leukemia. Sulanemadlin is a stapled peptide that mimics the N-terminal domain of p53, a tumor suppressor protein. As such, it binds to MDM2 and MDMX, leading to tumor cell apoptosis. Clinical trials Sulanemadlin is notable as the first stapled peptide, a novel pharmaceutical strategy, to enter clinical trials. Despite its preclinical promise, concerns about side effects, including severe neutropenia Neutropenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria ..., have terminated Phase 1B clinical trials early in at least one trial. References {{reflist P ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Stapled Peptide
A stapled peptide is a modified peptide (class A peptidomimetic), typically in an alpha-helical conformation, that is constrained by a synthetic brace ("staple"). The staple is formed by a covalent linkage between two amino acid side-chains, forming a peptide macrocycle. Staples, generally speaking, refer to a covalent linkage of two previously independent entities. Peptides with multiple, tandem staples are sometimes referred to as stitched peptides. Among other applications, peptide stapling is notably used to enhance the pharmacologic performance of peptides. Introduction The two primary classes of therapeutics are small molecules and protein therapeutics. The design of small molecule inhibitors of protein-protein interactions has been impeded by issues such as the general lack of small-molecule starting points for drug design, the typical flatness of the interface, the difficulty of distinguishing real from artifactual binding, and the size and character of typical small-mole ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Drug Development
Drug development is the process of bringing a new pharmaceutical drug to the market once a lead compound has been identified through the process of drug discovery. It includes preclinical research on microorganisms and animals, filing for regulatory status, such as via the United States Food and Drug Administration for an investigational new drug to initiate clinical trials on humans, and may include the step of obtaining regulatory approval with a new drug application to market the drug. The entire process—from concept through preclinical testing in the laboratory to clinical trial development, including Phase I–III trials—to approved vaccine or drug typically takes more than a decade. New chemical entity development Broadly, the process of drug development can be divided into preclinical and clinical work. Pre-clinical New chemical entities (NCEs, also known as new molecular entities or NMEs) are compounds that emerge from the process of drug discovery. These h ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Clinical Trials
Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, pharmaceutical drug, drugs, medical nutrition therapy, dietary choices, dietary supplements, and medical devices) and known interventions that warrant further study and comparison. Clinical trials generate data on dosage, safety and efficacy. They are conducted only after they have received institutional review board, health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial—their approval does not mean the therapy is 'safe' or effective, only that the trial may be conducted. Depending on product type and development stage, investigators initially enroll volunteers or patients into small Pilot experiment, pi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Myelodysplastic Syndrome
A myelodysplastic syndrome (MDS) is one of a group of cancers in which blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may include fatigue, shortness of breath, bleeding disorders, anemia, or frequent infections. Some types may develop into acute myeloid leukemia. Risk factors include previous chemotherapy or radiation therapy, exposure to certain chemicals such as tobacco smoke, pesticides, and benzene, and exposure to heavy metals such as Mercury (element), mercury or lead. Problems with blood cell formation result in some combination of low anemia, red blood cell, thrombocytopenia, platelet, and white blood cell counts. Some types of MDS cause an increase in the production of immature blood cells (called blast cell, blasts), in the bone marrow or peripheral blood, blood. The different types of MDS are identified based on the specific characteristics of the chang ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with haematopoiesis, normal blood cell production. Symptoms may include Fatigue, feeling tired, shortness of breath, Bruise, easy bruising and bleeding, and increased risk of infection. Occasionally, spread may occur to the brain, skin, or gums. As an acute leukemia, AML progresses rapidly, and is typically fatal within weeks or months if left untreated. Risk factors include getting older, being male, smoking, previous chemotherapy or radiation therapy, myelodysplastic syndrome, and exposure to the chemical benzene. The underlying mechanism involves replacement of normal bone marrow with leukemia cells, which results in a anemia, drop in red blood cells, thrombocytopenia, platelets, and normal leukopenia, white blood cells. Diagnosis is generally based on bone marrow aspiration and specific bl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
N-terminal
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amine group is bonded to the carboxylic group of another amino acid, making it a chain. That leaves a free carboxylic group at one end of the peptide, called the C-terminus, and a free amine group on the other end called the N-terminus. By convention, peptide sequences are written N-terminus to C-terminus, left to right (in LTR writing systems). This correlates the translation direction to the text direction, because when a protein is translated from messenger RNA, it is created from the N-terminus to the C-terminus, as amino acids are added to the carboxyl end of the protein. Chemistry Each amino acid has an amine group and a carboxylic group. Amino acids link to one another by peptide bonds which form through a dehydration reaction that j ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Murine Double Minute X
The Old World rats and mice, part of the subfamily Murinae in the family Muridae, comprise at least 519 species. Members of this subfamily are called murines. In terms of species richness, this subfamily is larger than all mammal families except the Cricetidae and Muridae, and is larger than all mammal orders except the bats and the remainder of the rodents. Description The Murinae are native to Africa, Europe, Asia, and Australia. They are terrestrial placental mammals. They have also been introduced to all continents except Antarctica, and are serious pest animals. This is particularly true in island communities where they have contributed to the endangerment and extinction of many native animals. Two prominent murine species have become vital laboratory animals: the brown rat and house mouse are both used as medical subjects. The murines have a distinctive molar pattern that involves three rows of cusps instead of two, the primitive pattern seen most frequently in mu ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Apoptosis
Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biology), morphology) and death. These changes include Bleb (cell biology), blebbing, Plasmolysis, cell shrinkage, Karyorrhexis, nuclear fragmentation, Pyknosis, chromatin condensation, Apoptotic DNA fragmentation, DNA fragmentation, and mRNA decay. The average adult human loses 50 to 70 1,000,000,000, billion cells each day due to apoptosis. For the average human child between 8 and 14 years old, each day the approximate loss is 20 to 30 billion cells. In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular injury, apoptosis is a highly regulated and controlled process that confers advantages during an organism's life cycle. For example, the separation of fingers and toes in a developing human embryo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
National Cancer Institute
The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. The NCI conducts and supports research, training, health information dissemination, and other activities related to the causes, prevention, diagnosis, and treatment of cancer; the supportive care of cancer patients and their families; and cancer survivorship. NCI is the oldest and has the largest budget and research program of the 27 institutes and centers of the NIH ($6.9 billion in 2020). It fulfills the majority of its mission via an extramural program that provides grants for cancer research. Additionally, the National Cancer Institute has intramural research programs in Bethesda, Maryland, and at the Frederick National Laboratory for Cancer Research at Fort Detrick in Frederick, Maryland. The NCI receives more than in funding e ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Neutropenia
Neutropenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria, bacterial fragments and immunoglobulin-bound viruses in the blood. People with neutropenia are more susceptible to bacterial infections and, without prompt medical attention, the condition may become life-threatening (neutropenic sepsis). Neutropenia can be divided into congenital and acquired, with severe congenital neutropenia (SCN) and cyclic neutropenia (CyN) being autosomal dominant and mostly caused by heterozygous mutations in the ELANE gene ( neutrophil elastase). Neutropenia can be acute (temporary) or chronic (long lasting). The term is sometimes used interchangeably with "leukopenia" ("deficit in the number of white blood cells"). Decreased production of neutrophils is associated with deficiencies of vitamin B12 and fol ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Peptide Therapeutics
Peptide therapeutics are peptides or polypeptides (oligomers or short polymers of amino acids) which are used to for the treatment of diseases. Naturally occurring peptides may serve as hormones, growth factors, neurotransmitters, ion channel ligands, and anti-infectives; peptide therapeutics mimic such functions. Peptide Therapeutics are seen as relatively safe and well-tolerated as peptides can be Metabolism, metabolized by the body. Examples The current highest selling marketed diabetic drug Liraglutide, incorporates a lipid chain to extend plasma circulation and prolong bioavailability. Liraglutide is a GLP-1 agonist drug that Self-assembly, self-assembles into an alpha-helical structure, and it requires once a day administration. Lipid conjugation of a palmitoyl chain to a lysine residue at position 26 of Liraglutide results in an extended half-life (around 13–14 hours) in the blood. This is due to the palmitoyl chain allowing non covalent binding to albumin, which delays p ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
