The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

cc-58     2-morpholin-4-yl-8-phenyl- chromen-4-one

Synonyms: PubChem16766, SureCN94377, AG-E-02402, CHEBI:65329, CS-0150, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of K00235

  • In contrast, beta(2)-AR (but not beta(1)-AR) stimulation elevated the activity of Akt, a powerful survival signal; this effect was fully abolished by inhibiting G(i), G(beta gamma), or phosphoinositide 3 kinase (PI3K) with pertussis toxin, beta ARK-ct (a peptide inhibitor of G(beta gamma)), or LY294002, respectively [1].
  • The effects of PDGF/IL-1beta costimulation on contractile marker expression and Akt and p70S6K phosphorylation were blocked by the phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 and by adenovirus expressing a dominant-negative Akt, and they were mimicked by constitutively active Akt [2].
  • Pre- and posttreatments with the AM receptor antagonist AM22-52 and PI3 kinase inhibitors (LY294002 and Wortmannin) significantly blocked or reversed AM-induced heat hyperalgesia [3].
  • A potential correlation between angiotensin-mediated PI3K activation and SMC growth was found using LY294002, a specific inhibitor of PI3K, which blocked the increase in DNA and RNA synthesis as well as cellular hyperplasia generated by Ang II (10(-6) mol/L) stimulation of quiescent SMCs [4].
  • Two weeks after i.p. inoculation with OVCAR-3 ovarian cancer cells, mice were treated i.p. with LY294002 plus paclitaxel, each three times weekly on alternate days, for 4 weeks [5].

Psychiatry related information on K00235

  • In contrast, LY294002-treated cells exhibited none of these myogenic characteristics and maintained high levels of Id, a negative regulator of myogenesis [6].

High impact information on K00235


Chemical compound and disease context of K00235


Biological context of K00235

  • The specific phosphoinositide 3-kinase (PI3K) inhibitors wortmannin and LY294002 have been invaluable tools for elucidating the roles of these enzymes in signal transduction pathways [17].
  • Akt-1 was constitutively activated in human macrophages and addition of the PI3K inhibitor, LY294002, suppressed the activation of Akt-1 and induced cell death [18].
  • Experiments in 3T3-L1 preadipocytes and adipocytes revealed that insulin-stimulated phosphorylation of Ser307 was inhibited by LY294002 or wortmannin, whereas TNF-alpha-stimulated phosphorylation was inhibited by PD98059 [19].
  • Finally, the phosphatidylinositol 3-kinase (PI(3)K) inhibitor LY294002 affects the frequency of pseudopod generation, but not the accuracy of selection, suggesting that PI(3)K regulates the underlying mechanism of cell movement, rather than control of direction [20].
  • Albumin endocytosis was inhibited by both wortmannin (IC50 6.9 nM) and LY294002 (IC50 6.5 microM) at concentrations that suggested the involvement of PI 3-kinase in its regulation [21].

Anatomical context of K00235


Associations of K00235 with other chemical compounds

  • IEC-6 cells were treated with LPS +/- LY294002 or wortmannin, and beta 1- and alpha 3-integrins were assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunofluorescence [26].
  • Both wortmannin and LY294002 prevent tyrosine phosphorylation, and membrane translocation of PLCgamma as well as IP(3) generation in ATP-stimulated cells [27].
  • The activity of Vps34p kinase is significantly reduced by the PI 3-kinase inhibitors wortmannin, a fungal metabolite, and LY294002, a quercetin analog (Stack, J. H., and S. D. Emr. 1994. J. Biol. Chem. 269:31552-31562) [28].
  • Protracted treatment with selective PI 3-K inhibitors, wortmannin and LY294002, abolished Akt-1 activity and induced neuronal death that could be reduced by long-term lithium pretreatment [29].
  • ATP-dependent transport of taurocholate and dinitrophenyl-glutathione in isolated canalicular vesicles from rat liver was reduced 50-70% by PI 3-kinase inhibitors, wortmannin, and LY294002, at concentrations that are specific for Type I PI 3-kinase [30].

Gene context of K00235

  • HGF/SF-induced branching was abrogated by the PI3 kinase inhibitors wortmannin and LY294002 [31].
  • Treatment with LY294002 or introduction of dn-Akt severely diminished DNA binding of Runx2 and Runx2-dependent transcription, whereas forced expression of myrAkt enhanced them [32].
  • In addition, the effect of PTEN on p27(KIP1) and the cell cycle can be mimicked by treatment of U87MG cells with LY294002, a selective inhibitor of PI 3-kinase [33].
  • In CHO-K1 cells expressing AFX-GFP, DNA fragmentation was induced by the stable PI 3-kinase inhibitor LY294002, and the expression of the active form of PKB suppressed this DNA fragmentation [34].
  • VEGF mRNA levels are decreased in cells treated with the PI 3-kinase inhibitor LY294002 and restored by overexpression of v-P3k or Myr-Akt [35].

Analytical, diagnostic and therapeutic context of K00235


  1. Dual modulation of cell survival and cell death by beta(2)-adrenergic signaling in adult mouse cardiac myocytes. Zhu, W.Z., Zheng, M., Koch, W.J., Lefkowitz, R.J., Kobilka, B.K., Xiao, R.P. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  2. Synergistic roles of platelet-derived growth factor-BB and interleukin-1beta in phenotypic modulation of human aortic smooth muscle cells. Chen, C.N., Li, Y.S., Yeh, Y.T., Lee, P.L., Usami, S., Chien, S., Chiu, J.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  3. A role for adrenomedullin as a pain-related peptide in the rat. Ma, W., Chabot, J.G., Quirion, R. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  4. Angiotensin II activates phosphatidylinositol 3-kinase in vascular smooth muscle cells. Saward, L., Zahradka, P. Circ. Res. (1997) [Pubmed]
  5. Inhibition of phosphatidylinositol 3'-kinase increases efficacy of paclitaxel in in vitro and in vivo ovarian cancer models. Hu, L., Hofmann, J., Lu, Y., Mills, G.B., Jaffe, R.B. Cancer Res. (2002) [Pubmed]
  6. Phosphatidylinositol 3-kinase inhibitors block differentiation of skeletal muscle cells. Kaliman, P., Viñals, F., Testar, X., Palacín, M., Zorzano, A. J. Biol. Chem. (1996) [Pubmed]
  7. Colonic polyposis caused by mTOR-mediated chromosomal instability in Apc+/Delta716 Cdx2+/- compound mutant mice. Aoki, K., Tamai, Y., Horiike, S., Oshima, M., Taketo, M.M. Nat. Genet. (2003) [Pubmed]
  8. Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor. Yao, R., Cooper, G.M. Science (1995) [Pubmed]
  9. Pivotal role of phosphoinositide-3 kinase in regulation of cytotoxicity in natural killer cells. Jiang, K., Zhong, B., Gilvary, D.L., Corliss, B.C., Hong-Geller, E., Wei, S., Djeu, J.Y. Nat. Immunol. (2000) [Pubmed]
  10. Binding and phosphorylation of par-4 by akt is essential for cancer cell survival. Goswami, A., Burikhanov, R., de Thonel, A., Fujita, N., Goswami, M., Zhao, Y., Eriksson, J.E., Tsuruo, T., Rangnekar, V.M. Mol. Cell (2005) [Pubmed]
  11. Control of cell polarity and chemotaxis by Akt/PKB and PI3 kinase through the regulation of PAKa. Chung, C.Y., Potikyan, G., Firtel, R.A. Mol. Cell (2001) [Pubmed]
  12. Signal transduction pathways involved in soluble fractalkine-induced monocytic cell adhesion. Cambien, B., Pomeranz, M., Schmid-Antomarchi, H., Millet, M.A., Breittmayer, V., Rossi, B., Schmid-Alliana, A. Blood (2001) [Pubmed]
  13. Combinatorial efficacy achieved through two-point blockade within a signaling pathway-a chemical genetic approach. Fan, Q.W., Specht, K.M., Zhang, C., Goldenberg, D.D., Shokat, K.M., Weiss, W.A. Cancer Res. (2003) [Pubmed]
  14. Activation of phosphoinositide 3-kinases by the CCR4 ligand macrophage-derived chemokine is a dispensable signal for T lymphocyte chemotaxis. Cronshaw, D.G., Owen, C., Brown, Z., Ward, S.G. J. Immunol. (2004) [Pubmed]
  15. Expression of cyclooxygenase-2 is regulated by glycogen synthase kinase-3beta in gastric cancer cells. Thiel, A., Heinonen, M., Rintahaka, J., Hallikainen, T., Hemmes, A., Dixon, D.A., Haglund, C., Ristimäki, A. J. Biol. Chem. (2006) [Pubmed]
  16. The PI3K inhibitor LY294002 blocks drug export from resistant colon carcinoma cells overexpressing MRP1. Abdul-Ghani, R., Serra, V., Györffy, B., Jürchott, K., Solf, A., Dietel, M., Schäfer, R. Oncogene (2006) [Pubmed]
  17. Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Walker, E.H., Pacold, M.E., Perisic, O., Stephens, L., Hawkins, P.T., Wymann, M.P., Williams, R.L. Mol. Cell (2000) [Pubmed]
  18. Constitutively activated Akt-1 is vital for the survival of human monocyte-differentiated macrophages. Role of Mcl-1, independent of nuclear factor (NF)-kappaB, Bad, or caspase activation. Liu, H., Perlman, H., Pagliari, L.J., Pope, R.M. J. Exp. Med. (2001) [Pubmed]
  19. Insulin/IGF-1 and TNF-alpha stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways. Rui, L., Aguirre, V., Kim, J.K., Shulman, G.I., Lee, A., Corbould, A., Dunaif, A., White, M.F. J. Clin. Invest. (2001) [Pubmed]
  20. Chemotaxis in shallow gradients is mediated independently of PtdIns 3-kinase by biased choices between random protrusions. Andrew, N., Insall, R.H. Nat. Cell Biol. (2007) [Pubmed]
  21. Receptor-mediated endocytosis of albumin by kidney proximal tubule cells is regulated by phosphatidylinositide 3-kinase. Brunskill, N.J., Stuart, J., Tobin, A.B., Walls, J., Nahorski, S. J. Clin. Invest. (1998) [Pubmed]
  22. 1alpha,25-dihydroxyvitamin D(3)-induced myeloid cell differentiation is regulated by a vitamin D receptor-phosphatidylinositol 3-kinase signaling complex. Hmama, Z., Nandan, D., Sly, L., Knutson, K.L., Herrera-Velit, P., Reiner, N.E. J. Exp. Med. (1999) [Pubmed]
  23. Mechanisms of acute eosinophil mobilization from the bone marrow stimulated by interleukin 5: the role of specific adhesion molecules and phosphatidylinositol 3-kinase. Palframan, R.T., Collins, P.D., Severs, N.J., Rothery, S., Williams, T.J., Rankin, S.M. J. Exp. Med. (1998) [Pubmed]
  24. Role of phosphatidylinositol 3-kinase in the development of hepatocyte preconditioning. Carini, R., Grazia De Cesaris, M., Splendore, R., Baldanzi, G., Nitti, M.P., Alchera, E., Filigheddu, N., Domenicotti, C., Pronzato, M.A., Graziani, A., Albano, E. Gastroenterology (2004) [Pubmed]
  25. Regulatory role of phosphatidylinositol 3-kinase on TNF-alpha-induced cyclooxygenase 2 expression in colonic epithelial cells. Weaver, S.A., Russo, M.P., Wright, K.L., Kolios, G., Jobin, C., Robertson, D.A., Ward, S.G. Gastroenterology (2001) [Pubmed]
  26. Increased expression and function of integrins in enterocytes by endotoxin impairs epithelial restitution. Qureshi, F.G., Leaphart, C., Cetin, S., Li, J., Grishin, A., Watkins, S., Ford, H.R., Hackam, D.J. Gastroenterology (2005) [Pubmed]
  27. A specific role of phosphatidylinositol 3-kinase gamma. A regulation of autonomic Ca(2)+ oscillations in cardiac cells. Bony, C., Roche, S., Shuichi, U., Sasaki, T., Crackower, M.A., Penninger, J., Mano, H., Pucéat, M. J. Cell Biol. (2001) [Pubmed]
  28. Role for phosphatidylinositol 3-kinase in the sorting and transport of newly synthesized lysosomal enzymes in mammalian cells. Brown, W.J., DeWald, D.B., Emr, S.D., Plutner, H., Balch, W.E. J. Cell Biol. (1995) [Pubmed]
  29. Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neurons. Chalecka-Franaszek, E., Chuang, D.M. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  30. Phosphoinositide 3-kinase lipid products regulate ATP-dependent transport by sister of P-glycoprotein and multidrug resistance associated protein 2 in bile canalicular membrane vesicles. Misra, S., Ujházy, P., Varticovski, L., Arias, I.M. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  31. Reconstitution of mammary gland development in vitro: requirement of c-met and c-erbB2 signaling for branching and alveolar morphogenesis. Niemann, C., Brinkmann, V., Spitzer, E., Hartmann, G., Sachs, M., Naundorf, H., Birchmeier, W. J. Cell Biol. (1998) [Pubmed]
  32. Runx2 induces osteoblast and chondrocyte differentiation and enhances their migration by coupling with PI3K-Akt signaling. Fujita, T., Azuma, Y., Fukuyama, R., Hattori, Y., Yoshida, C., Koida, M., Ogita, K., Komori, T. J. Cell Biol. (2004) [Pubmed]
  33. PTEN/MMAC1/TEP1 suppresses the tumorigenicity and induces G1 cell cycle arrest in human glioblastoma cells. Li, D.M., Sun, H. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  34. Regulation of nuclear translocation of forkhead transcription factor AFX by protein kinase B. Takaishi, H., Konishi, H., Matsuzaki, H., Ono, Y., Shirai, Y., Saito, N., Kitamura, T., Ogawa, W., Kasuga, M., Kikkawa, U., Nishizuka, Y. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  35. Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells. Jiang, B.H., Zheng, J.Z., Aoki, M., Vogt, P.K. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  36. Reversal of the Ras-induced transformed phenotype by HR12, a novel ras farnesylation inhibitor, is mediated by the Mek/Erk pathway. Reuveni, H., Geiger, T., Geiger, B., Levitzki, A. J. Cell Biol. (2000) [Pubmed]
  37. Interleukin-2-induced survival of natural killer (NK) cells involving phosphatidylinositol-3 kinase-dependent reduction of ceramide through acid sphingomyelinase, sphingomyelin synthase, and glucosylceramide synthase. Taguchi, Y., Kondo, T., Watanabe, M., Miyaji, M., Umehara, H., Kozutsumi, Y., Okazaki, T. Blood (2004) [Pubmed]
  38. Cytochrome p450 epoxygenase metabolism of arachidonic acid inhibits apoptosis. Chen, J.K., Capdevila, J., Harris, R.C. Mol. Cell. Biol. (2001) [Pubmed]
  39. The phosphoinositide 3-kinase/Akt pathway: a new target in human renal cell carcinoma therapy. Sourbier, C., Lindner, V., Lang, H., Agouni, A., Schordan, E., Danilin, S., Rothhut, S., Jacqmin, D., Helwig, J.J., Massfelder, T. Cancer Res. (2006) [Pubmed]
  40. The phosphatidylinositol 3'-kinase pathway is a dominant growth factor-activated cell survival pathway in LNCaP human prostate carcinoma cells. Lin, J., Adam, R.M., Santiestevan, E., Freeman, M.R. Cancer Res. (1999) [Pubmed]
WikiGenes - Universities