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| Other names | DS-3032 |
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| Formula | C30H34Cl2FN5O4 |
| Molar mass | 618.53 g·mol−1 |
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Milademetan is an investigational new drug that is being evaluated to treat liposarcoma. [1] It is a MDM2 inhibitor. [2]
p53, also known as Tumor protein P53, cellular tumor antigen p53, or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins are crucial in vertebrates, where they prevent cancer formation. As such, p53 has been described as "the guardian of the genome" because of its role in conserving stability by preventing genome mutation. Hence TP53 is classified as a tumor suppressor gene.
Alopecia universalis(AU), also known as alopecia areata universalis, is a medical condition involving the loss of all body hair, including eyebrows, eyelashes, chest hair, armpit hair, and pubic hair. It is the most severe form of alopecia areata (AA). People with the condition are usually healthy and have no other symptoms and a normal life expectancy.
Desquamation, or peeling skin, is the shedding of dead cells from the outermost layer of skin.
2-Imidazoline (Preferred IUPAC name: 4,5-dihydro-1H-imidazole) is one of three isomers of the nitrogen-containing heterocycle imidazoline, with the formula C3H6N2. The 2-imidazolines are the most common imidazolines commercially, as the ring exists in some natural products and some pharmaceuticals. They also have been examined in the context of organic synthesis, coordination chemistry, and homogeneous catalysis.
Mouse double minute 2 homolog (MDM2) also known as E3 ubiquitin-protein ligase Mdm2 is a protein that in humans is encoded by the MDM2 gene. Mdm2 is an important negative regulator of the p53 tumor suppressor. Mdm2 protein functions both as an E3 ubiquitin ligase that recognizes the N-terminal trans-activation domain (TAD) of the p53 tumor suppressor and as an inhibitor of p53 transcriptional activation.
p14ARF is an alternate reading frame protein product of the CDKN2A locus. p14ARF is induced in response to elevated mitogenic stimulation, such as aberrant growth signaling from MYC and Ras (protein). It accumulates mainly in the nucleolus where it forms stable complexes with NPM or Mdm2. These interactions allow p14ARF to act as a tumor suppressor by inhibiting ribosome biogenesis or initiating p53-dependent cell cycle arrest and apoptosis, respectively. p14ARF is an atypical protein, in terms of its transcription, its amino acid composition, and its degradation: it is transcribed in an alternate reading frame of a different protein, it is highly basic, and it is polyubiquinated at the N-terminus.
p16, is a protein that slows cell division by slowing the progression of the cell cycle from the G1 phase to the S phase, thereby acting as a tumor suppressor. It is encoded by the CDKN2A gene. A deletion in this gene can result in insufficient or non-functional p16, accelerating the cell cycle and resulting in many types of cancer.
PDE3 is a phosphodiesterase. The PDEs belong to at least eleven related gene families, which are different in their primary structure, substrate affinity, responses to effectors, and regulation mechanism. Most of the PDE families are composed of more than one gene. PDE3 is clinically significant because of its role in regulating heart muscle, vascular smooth muscle and platelet aggregation. PDE3 inhibitors have been developed as pharmaceuticals, but their use is limited by arrhythmic effects and they can increase mortality in some applications.
Acute myeloblastic leukemia with maturation (M2) is a subtype of acute myeloid leukemia (AML).
Karen Heather Vousden, CBE, FRS, FRSE, FMedSci is a British medical researcher. She is known for her work on the tumour suppressor protein, p53, and in particular her discovery of the important regulatory role of Mdm2, an attractive target for anti-cancer agents. From 2003 to 2016, she was the director of the Cancer Research UK Beatson Institute in Glasgow, UK, moving back to London in 2016 to take up the role of Chief Scientist at CRUK and Group Leader at the Francis Crick Institute.
Protein Mdm4 is a protein that in humans is encoded by the MDM4 gene.
Tesaglitazar is a dual peroxisome proliferator-activated receptor agonist with affinity to PPARα and PPARγ, proposed for the management of type 2 diabetes.
W-18 is a compound in a series of 32 substances that were first synthesized in academic research on analgesic drug discovery in the 1980s and appeared as a designer drug in the 2010s.
Nutlins are cis-imidazoline analogs which inhibit the interaction between mdm2 and tumor suppressor p53, and which were discovered by screening a chemical library by Vassilev et al. Nutlin-1, nutlin-2, and nutlin-3 were all identified in the same screen; however, Nutlin-3 is the compound most commonly used in anti-cancer studies. Nutlin small molecules occupy p53 binding pocket of MDM2 and effectively disrupt the p53–MDM2 interaction that leads to activation of the p53 pathway in p53 wild-type cells. Inhibiting the interaction between mdm2 and p53 stabilizes p53, and is thought to selectively induce a growth-inhibiting state called senescence in cancer cells. These compounds are therefore thought to work best on tumors that contain normal or "wild-type" p53. Nutlin-3 has been shown to affect the production of p53 within minutes.
KRT77 encodes keratin 77, a member of the type II keratin family of intermediate filament proteins. Keratin 77 is also known as KRT1B, Type II cytoskeletal 1b, Type II keratin Kb39, and cytokeratin 1B. KRT77 is well-expressed by granular layer epidermal keratinocytes except for those that reside at acral surfaces. There is little to no expression of KRT77 in acral keratinocytes.
Tofacitinib, sold under the brand Xeljanz among others, is a medication used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, polyarticular course juvenile idiopathic arthritis, and ulcerative colitis. It is a janus kinase (JAK) inhibitor, discovered and developed by the National Institutes of Health and Pfizer.
Lympho-epithelial Kazal-type related inhibitor 2 (LEKTI-2) is a protein encoded by the SPINK9 gene in humans. SPINK9 is a member of a gene family cluster located on chromosome 5q33.1, which includes SPINK5 and SPINK6. LEKTI-2 is an inhibitor of KLK5.
Shaomeng Wang is a Chinese-American chemist currently the Warner-Lambert/Parke-Davis Professor in Medicine at University of Michigan and a former Co-Editor-in-Chief at American Chemical Society's Journal of Medicinal Chemistry. A cited expert in his field, his interests are synthesis and design of moleculars, neurological diseases and computational and informatics. He was Elected as Fellow at the National Academy of Inventors in 2014. Dr. Wang was named to the AAAS Fellows Section on Pharmaceutical Sciences in 2019, and is the recipient of the Division of Medicinal Chemistry Award 2020 American Chemical Society.
Brigimadlin (BI-907828) is a small molecule MDM2-TP53 inhibitor developed for liposarcoma.
Zevaquenabant is an investigational small-molecule drug, discovered by the National Institutes of Health. Zevaquenabant was described as a third generation cannabinoid receptor 1 (CB1R) antagonist due to its peripheral selectivity and polypharmacology. It acts as a peripherally selective inverse agonist of the cannabinoid receptor 1 and an inducible nitric oxide synthase (iNOS) inhibitor. It has been studied in the experimental models of fibrotic disorders such as liver fibrosis[1], chronic kidney disease, idiopathic pulmonary fibrosis, Hermansky-Pudlak syndrome pulmonary fibrosis, skin fibrosis, and metabolic disorders such as obesity[2] and dyslipidemia.
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