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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, ...
 
 
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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

References

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  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]
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  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]
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  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]
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  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]
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  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]
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