Wortmannin

Wortmannin
Names
IUPAC name
1α-(Methoxymethyl)-3,7,17-trioxo-2-oxa-6,4-(epoxymetheno)androsta-5,8-dien-11α-yl acetate
Systematic IUPAC name
(1S,6bR,9aS,11R,11bR)-1-(Methoxymethyl)-9a,11b-dimethyl-3,6,9-trioxo-1,6,6b,7,8,9,9a,10,11,11b-decahydro-3H-furo[4,3,2-de]indeno[4,5-h][2]benzopyran-11-yl acetate
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.112.065 Edit this at Wikidata
UNII
  • InChI=1S/C23H24O8/c1-10(24)30-13-7-22(2)12(5-6-14(22)25)16-18(13)23(3)15(9-28-4)31-21(27)11-8-29-20(17(11)23)19(16)26/h8,12-13,15H,5-7,9H2,1-4H3/t12-,13+,15+,22-,23-/m0/s1 ☒N
    Key: QDLHCMPXEPAAMD-QAIWCSMKSA-N ☒N
  • O=C\3c2occ1C(=O)O[C@@H]([C@@](c12)(/C5=C/3[C@H]4[C@](C(=O)CC4)(C)C[C@H]5OC(=O)C)C)COC
Properties
C23H24O8
Molar mass 428.437 g·mol−1
Melting point 238 to 242 °C (460 to 468 °F; 511 to 515 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Wortmannin, a steroid metabolite of the fungi Penicillium funiculosum, Talaromyces wortmannii, is a non-specific, covalent inhibitor of phosphoinositide 3-kinases (PI3Ks). It has an in vitro inhibitory concentration (IC50) of around 5 nM, making it a more potent inhibitor than LY294002, another commonly used PI3K inhibitor. It displays a similar potency in vitro for the class I, II, and III PI3K members although it can also inhibit other PI3K-related enzymes such as mTOR, DNA-PKcs, some phosphatidylinositol 4-kinases, myosin light chain kinase (MLCK) and mitogen-activated protein kinase (MAPK) at high concentrations[1][2] Wortmannin has also been reported to inhibit members of the polo-like kinase family with IC50 in the same range as for PI3K.[3] The half-life of wortmannin in tissue culture is about 10 minutes due to the presence of the highly reactive C20 carbon that is also responsible for its ability to covalently inactivate PI3K. Wortmannin is a commonly used cell biology reagent that has been used previously in research to inhibit DNA repair, receptor-mediated endocytosis and cell proliferation.[4][5]

  1. ^ Vanhaesebroeck B, Leevers SJ, Ahmadi K, Timms J, Katso R, Driscoll PC, et al. (2001). "Synthesis and function of 3-phosphorylated inositol lipids". Annual Review of Biochemistry. 70: 535–602. doi:10.1146/annurev.biochem.70.1.535. PMID 11395417.
  2. ^ Ferby I, Waga I, Kume K, Sakanaka C, Shimizu T (1996). "PAF-Induced MAPK Activation is Inhibited by Wortmannin in Neutrophils and Macrophages". Platelet-Activating Factor and Related Lipid Mediators 2. Advances in Experimental Medicine and Biology. Vol. 416. pp. 321–6. doi:10.1007/978-1-4899-0179-8_51. ISBN 978-1-4899-0181-1. PMID 9131167.
  3. ^ Liu Y, Jiang N, Wu J, Dai W, Rosenblum JS (January 2007). "Polo-like kinases inhibited by wortmannin. Labeling site and downstream effects". The Journal of Biological Chemistry. 282 (4): 2505–11. doi:10.1074/jbc.M609603200. PMID 17135248.
  4. ^ Liu Y, Shreder KR, Gai W, Corral S, Ferris DK, Rosenblum JS (January 2005). "Wortmannin, a widely used phosphoinositide 3-kinase inhibitor, also potently inhibits mammalian polo-like kinase". Chemistry & Biology. 12 (1): 99–107. doi:10.1016/j.chembiol.2004.11.009. PMID 15664519.
  5. ^ Kim SH, Jang YW, Hwang P, Kim HJ, Han GY, Kim CW (January 2012). "The reno-protective effect of a phosphoinositide 3-kinase inhibitor wortmannin on streptozotocin-induced proteinuric renal disease rats". Experimental & Molecular Medicine. 44 (1): 45–51. doi:10.3858/emm.2012.44.1.004. PMC 3277897. PMID 22056625.