12-O-Tetradecanoylphorbol-13-acetate

changed changed 477208864 12-O-Tetradecanoylphorbol-13-acetate 12-O-Tetradecanoylphorbol-13-acetate.svg 300px TPA (1aR,1bS,4aR,7aS,7bS,8R,9R,9aS)-4a,7b-Dihydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-5-oxo-1,1a,1b,4,4a,5,7a,7b,8,9-decahydro-9aH-cyclopropa[3,4]benzo[1,2-e]azulene-9,9a-diyl 9a-acetate 9-tetradecanoate TPA, PMA, Phorbol myristate acetate,Tetradecanoylphorbol acetate. 2341 27924 changed chemspider 25977 changed EBI 37537 CCCCCCCCCCCCCC(=O)O[C@@H]1[C@H]([C@]2([C@@H](C=C(C[C@]3([C@H]2C=C(C3=O)C)O)CO)[C@H]4[C@@]1(C4(C)C)OC(=O)C)O)C CCCCCCCCCCCCCC(=O)O[C@@H]2C(C)[C@]1(O)C4/C=C(/C)C(=O)[C@@]4(O)CC(\CO)=C/[C@H]1[C@H]3[C@]2(OC(C)=O)C3(C)C 1/C36H56O8/c1-7-8-9-10-11-12-13-14-15-16-17-18-29(39)43-32-24(3)35(42)27(30-33(5,6)36(30,32)44-25(4)38)20-26(22-37)21-34(41)28(35)19-23(2)31(34)40/h19-20,24,27-28,30,32,37,41-42H,7-18,21-22H2,1-6H3/t24-,27+,28-,30-,32-,34-,35-,36-/m1/s1 PHEDXBVPIONUQT-RGYGYFBIBK changed chemspider 1S/C36H56O8/c1-7-8-9-10-11-12-13-14-15-16-17-18-29(39)43-32-24(3)35(42)27(30-33(5,6)36(30,32)44-25(4)38)20-26(22-37)21-34(41)28(35)19-23(2)31(34)40/h19-20,24,27-28,30,32,37,41-42H,7-18,21-22H2,1-6H3/t24-,27+,28-,30-,32-,34-,35-,36-/m1/s1 changed chemspider PHEDXBVPIONUQT-RGYGYFBISA-N correct CAS 16561-29-8 correct FDA NI40JAQ945 changed EBI 279115 changed kegg C05151 36 56 8 616.83 g/mol 12-O-Tetradecanoylphorbol-13-acetate (TPA), also commonly known as tetradecanoylphorbol acetate, tetradecanoyl phorbol acetate, and phorbol 12-myristate 13-acetate (PMA) is a diester of phorbol. It is a potent tumor promoter often employed in biomedical research to activate the signal transduction enzyme protein kinase C (PKC). Castagna 1982 Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters http://www.jbc.org/content/257/13/7847.full.pdf Journal of Biological Chemistry 257 13 7847–7851 10.1016/S0021-9258(18)34459-4 7085651 free Blumberg 1988 Protein kinase C as the receptor for the phorbol ester tumor promoters: sixth Rhoads memorial award lecture Cancer Research 48 1 1–8 3275491 Niedel 1983 Proceedings of the National Academy of Sciences 80 36–40 10.1073/pnas.80.1.36 Phorbol Diester Receptor Copurifies with Protein Kinase C 1 1983PNAS...80...36N 393304 6296873 free The effects of TPA on PKC result from its similarity to one of the natural activators of classic PKC isoforms, diacylglycerol. TPA is a small molecule drug. In ROS biology, superoxide was identified as the major reactive oxygen species induced by TPA/PMA but not by ionomycin in mouse macrophages. Swindle 2002 A Comparison of Reactive Oxygen Species Generation by Rat Peritoneal Macrophages and Mast Cells Using the Highly Sensitive Real-Time Chemiluminescent Probe Pholasin: Inhibition of Antigen-Induced Mast Cell Degranulation by Macrophage-Derived Hydrogen Peroxide http://www.jimmunol.org/content/169/10/5866.full.pdf The Journal of Immunology 169 10 5866–5873 10.4049/jimmunol.169.10.5866 12421969 21433304 free Thus, TPA/PMA has been routinely used as an inducer for endogenous superoxide production. Huang 2014 Megakaryocytic Differentiation of K562 Cells Induced by PMA Reduced the Activity of Respiratory Chain Complex IV PLoS ONE 9 5 e96246 10.1371/journal.pone.0096246 2014PLoSO...996246H 4015910 24817082 free TPA is also being studied as a drug in the treatment of hematologic cancer November 2015 TPA has a specific use in cancer diagnostics as a B-cell specific mitogen in cytogenetic testing. Cells must be divided in a cytogenic test to view the chromosomes. TPA is used to stimulate division of B-cells during cytogenetic diagnosis of B-cell cancers such as chronic lymphocytic leukemia.The AGT cytogenetics laboratory manual. 3rd ed. Barch, Margaret J., Knutsen, Turid., Spurbeck, Jack L., eds. 1997. Lippincott-Raven. TPA is also commonly used together with ionomycin to stimulate T-cell activation, proliferation, and cytokine production, and is used in protocols for intracellular staining of these cytokines. http://www.ebioscience.com/resources/best-protocols/flow-cytometry/flow-cytometry-intracellular-staining-quick-guide.htm Flow Cytometry Intracellular Staining Guide eBioscience, Inc 2011-09-25 2017-01-21 https://web.archive.org/web/20170121081102/http://www.ebioscience.com/resources/best-protocols/flow-cytometry/flow-cytometry-intracellular-staining-quick-guide.htm TPA induces KSHV reactivation in PEL cell cultures via stimulation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway. The pathway involves the activation of the early-immediate viral protein RTA that contributes to the activation of the lytic cycle.Cohen Adina Brodie Chaya Sarid Ronit An essential role of ERK signalling in TPA-induced reactivation of Kaposi's sarcoma-associated herpesvirus. The Journal of General Virology April 2006 87 Pt 4 795–802 16528027 10.1099/vir.0.81619-0 TPA was first found in the Croton plant, a shrub found in Southeast Asia, exposure to which provokes a poison ivy-like rash.December 2012 It underwent a phase 1 clinical trial.Schaar Dale Goodell Lauri Aisner Joseph Cui Xiao Xing Han Zheng Tao Chang Richard Martin John Grospe Stephanie Dudek Liesel Riley Joan Manago Jacqueline Lin Yong Rubin Eric H. Conney Allan Strair Roger K. A phase I clinical trial of 12- O-tetradecanoylphorbol-13-acetate for patients with relapsed/refractory malignancies Cancer Chemotherapy and Pharmacology June 2006 57 6 789–795 10.1007/s00280-005-0125-1 16231182 33377618 https://link.springer.com/article/10.1007/s00280-005-0125-1 en 1432-0843 subscription References External links Tetradecanoylphorbol+Acetate http://www.cancer.gov/dictionary?CdrID=46763 NCI Dictionary Entry 2005-07-02 http://www.clinicaltrials.gov/ct/show/NCT00004058 Phase 1 Clinical Trials 2005-07-02 Category:Diterpenes Category:Carcinogens Category:Acetate esters Category:Cyclopropanes Category:Cyclopentenes Category:Phorbol esters