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Triptolide
Triptolide is a diterpenoid epoxide which is produced by the thunder god vine, ''Tripterygium wilfordii''. It has ''in vitro'' and ''in vivo'' activities against mouse models of polycystic kidney disease and pancreatic cancer, but its physical properties and severe toxicity limit its therapeutic potential. Consequently, a synthetic water-soluble prodrug, minnelide, is being studied clinically instead. Triptolide is a component of ContraPest, a contraceptive pest control liquid used to reduce rat populations in the United States. Mechanism of action Several putative target proteins of triptolide have been reported, including polycystin-2, ADAM10, DCTPP1, TAB1, and XPB. Multiple triptolide-resistant mutations exist in XPB (ERCC3) and its partner protein GTF2H4.Y. Smurnyy, M. Cai, H. Wu, E. McWhinnie, J. A. Tallarico, Y.Yang, Y. Feng, DNA sequencing and CRISPR-Cas9 gene editing for target validation in mammalian cells. ''Nat. Chem. Biol''. 2014, 10, 623 – 625 However, no trip ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Minnelide Structure
Triptolide is a diterpenoid epoxide which is produced by the thunder god vine, ''Tripterygium wilfordii''. It has ''in vitro'' and ''in vivo'' activities against mouse models of polycystic kidney disease and pancreatic cancer, but its physical properties and severe toxicity limit its therapeutic potential. Consequently, a synthetic water-soluble prodrug, minnelide, is being studied clinically instead. Triptolide is a component of ContraPest, a contraceptive pest control liquid used to reduce rat populations in the United States. Mechanism of action Several putative target proteins of triptolide have been reported, including polycystin-2, ADAM10, DCTPP1, TAB1, and XPB. Multiple triptolide-resistant mutations exist in XPB (ERCC3) and its partner protein GTF2H4.Y. Smurnyy, M. Cai, H. Wu, E. McWhinnie, J. A. Tallarico, Y.Yang, Y. Feng, DNA sequencing and CRISPR-Cas9 gene editing for target validation in mammalian cells. ''Nat. Chem. Biol''. 2014, 10, 623 – 625 However, no trip ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tripterygium Wilfordii
''Tripterygium wilfordii'', or ''léi gōng téng'' (Mandarin) (, Japanese: ''raikōtō''), sometimes called thunder god vine but more properly translated thunder duke vine, is a vine used in traditional Chinese medicine. ''Tripterygium wilfordii'' has been promoted for use in rheumatoid arthritis and psoriasis; however, due to safety concerns this use is not recommended. Evidence is insufficient to deem it effective as a method of birth control for humans. A 2021 study published in Nature Communications found that one chemical isolated from the herb, triptonide, was an effective male birth control in mice and non-human primates, while others chemicals present in the herb have been previously shown to cause severe liver toxicity. Extracts of the bark T. wilfordii have been used as an insecticide in China for centuries, as documented in Wu Qijun’s 1848 Illustrated Catalogues of Plants. Health effects The United Kingdom government does not recommend the use of ''Tripterygium'' du ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Triptonide
Triptonide is a chemical compound found in ''Tripterygium wilfordii'', a plant used in traditional Chinese medicine Traditional Chinese medicine (TCM) is an alternative medical practice drawn from traditional medicine in China. It has been described as "fraught with pseudoscience", with the majority of its treatments having no logical mechanism of action .... A 2021 trial in mice and monkeys suggested that triptonide may offer a reversible male contraceptive. References {{organic-compound-stub Heterocyclic compounds with 7 or more rings Epoxides Lactones Isopropyl compounds Ketones Contraception for males ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Epoxides
In organic chemistry, an epoxide is a cyclic ether () with a three-atom ring. This ring approximates an equilateral triangle, which makes it strained, and hence highly reactive, more so than other ethers. They are produced on a large scale for many applications. In general, low molecular weight epoxides are colourless and nonpolar, and often volatile. Nomenclature A compound containing the epoxide functional group can be called an epoxy, epoxide, oxirane, and ethoxyline. Simple epoxides are often referred to as oxides. Thus, the epoxide of ethylene (C2H4) is ethylene oxide (C2H4O). Many compounds have trivial names; for instance, ethylene oxide is called "oxirane". Some names emphasize the presence of the epoxide functional group, as in the compound ''1,2-epoxyheptane'', which can also be called ''1,2-heptene oxide''. A polymer formed from epoxide precursors is called an ''epoxy'', but such materials do not contain epoxide groups (or contain only a few residual epoxy grou ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Diterpenes
Diterpenes are a class of chemical compounds composed of four isoprene units, often with the molecular formula C20H32. They are biosynthesized by plants, animals and fungi via the HMG-CoA reductase pathway, with geranylgeranyl pyrophosphate being a primary intermediate. Diterpenes form the basis for biologically important compounds such as retinol, retinal, and phytol. They are known to be antimicrobial and antiinflammatory. Structures As with most terpenes a huge number of potential structures exists, which may be broadly divided according to the number of rings present. Biosynthesis Diterpenes are derived from the addition of one IPP unit to FPP to form geranylgeranyl-pyrophosphate (GGPP). From GGPP, structural diversity is achieved mainly by two classes of enzymes; the diterpene synthases and cytochromes P450. Several diterpenes are produced by plants and cyanobacteria. GGPP is also the precursor for the synthesis of the phytane by the action of the enzyme geranylger ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phases Of Clinical Research
The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases start with testing for safety in a few human subjects, then expand to many study participants (potentially tens of thousands) to determine if the treatment is effective. Clinical research is conducted on drug candidates, vaccine candidates, new medical devices, and new diagnostic assays. Summary Clinical trials testing potential medical products are commonly classified into four phases. The drug development process will normally proceed through all four phases over many years. If the drug successfully passes through Phases I, II, and III, it will usually be approved by the national regulatory authority for use in the general population. Phase IV trials are 'post-marketing' or 'surveillance' studies conducted to monitor safety over sever ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Gemcitabine
Gemcitabine, with brand names including Gemzar, is a chemotherapy medication. It treats cancers including testicular cancer, breast cancer, ovarian cancer, non-small cell lung cancer, pancreatic cancer, and bladder cancer. It is administered by intravenous infusion. It acts against neoplastic growth, and it inhibits the replication of Orthohepevirus A, the causative agent of Hepatitis E, through upregulation of interferon signaling. Common side effects include bone marrow suppression, liver and kidney problems, nausea, fever, rash, shortness of breath, mouth sores, diarrhea, neuropathy, and hair loss. Use during pregnancy will likely result in fetal harm. Gemcitabine is in the nucleoside analog family of medication. It works by blocking the creation of new DNA, which results in cell death. Gemcitabine was patented in 1983 and was approved for medical use in 1995. Generic versions were introduced in Europe in 2009 and in the US in 2010. It is on the WHO Model List of Essentia ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Gene Regulatory Network
A gene (or genetic) regulatory network (GRN) is a collection of molecular regulators that interact with each other and with other substances in the cell to govern the gene expression levels of mRNA and proteins which, in turn, determine the function of the cell. GRN also play a central role in morphogenesis, the creation of body structures, which in turn is central to evolutionary developmental biology (evo-devo). The regulator can be DNA, RNA, protein or any combination of two or more of these three that form a complex, such as a specific sequence of DNA and a transcription factor to activate that sequence. The interaction can be direct or indirect (through transcribed RNA or translated protein). In general, each mRNA molecule goes on to make a specific protein (or set of proteins). In some cases this protein will be Protein#Structural proteins, structural, and will accumulate at the cell membrane or within the cell to give it particular structural properties. In other cases th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Super-enhancer
In genetics, a super-enhancer is a region of the mammalian genome comprising multiple enhancers that is collectively bound by an array of transcription factor proteins to drive transcription of genes involved in cell identity. Because super-enhancers are frequently identified near genes important for controlling and defining cell identity, they may thus be used to quickly identify key nodes regulating cell identity. Enhancers have several quantifiable traits that have a range of values, and these traits are generally elevated at super-enhancers. Super-enhancers are bound by higher levels of transcription-regulating proteins and are associated with genes that are more highly expressed. Expression of genes associated with super-enhancers is particularly sensitive to perturbations, which may facilitate cell state transitions or explain sensitivity of super-enhancer—associated genes to small molecules that target transcription. History The regulation of transcription by enhancers h ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GTF2H4
General transcription factor IIH subunit 4 is a protein that in humans is encoded by the ''GTF2H4'' gene. Interactions GTF2H4 has been shown to interact with: * GTF2F1, * MED21, * POLR2A, * TATA binding protein, * Transcription Factor II B, and * XPB. See also * Transcription Factor II H Transcription factor II Human (transcription factor II H; TFIIH) is an important protein complex, having roles in transcription of various protein-coding genes and DNA nucleotide excision repair (NER) pathways. TFIIH first came to light in 1989 ... References Further reading * * * * * * * * * * * * * * * * * External links * Transcription factors {{gene-6-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TAB1
Mitogen-activated protein kinase kinase kinase 7-interacting protein 1 is an enzyme that in humans is encoded by the ''TAB1'' gene. Function The protein encoded by this gene was identified as a regulator of the MAP kinase kinase kinase MAP3K7/TAK1, which is known to mediate various intracellular signaling pathways, such as those induced by TGF-beta, interleukin-1, and WNT-1. This protein interacts and thus activates TAK1 kinase. It has been shown that the C-terminal portion of this protein is sufficient for binding and activation of TAK1, while a portion of the N-terminus acts as a dominant-negative inhibitor of TGF beta, suggesting that this protein may function as a mediator between TGF beta receptors and TAK1. This protein can also interact with and activate the mitogen-activated protein kinase 14 (MAPK14/p38alpha), and thus represents an alternative activation pathway, in addition to the MAPKK pathways, which contributes to the biological responses of MAPK14 to various stimu ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
