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

Nutlin     4-[[4,5-bis(4-chlorophenyl)- 2-(4-methoxy-2...

Synonyms: Rac-Nutlin-3, Nutlin-3, nutlin 3, S1061_Selleck, AGN-PC-0090GA, ...
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 Nutlin-3


High impact information on Nutlin-3

  • Cancer cells with mdm2 gene amplification were most sensitive to nutlin-3 in vitro and in vivo, suggesting that MDM2 overexpression may be the only abnormality in the p53 pathway of these cells [5].
  • The induction of p53 by nutlin-3 in B-CLL samples was accompanied by alterations of the mitochondrial potential and activation of the caspase-dependent apoptotic pathway [2].
  • Normal human T cells showed lower sensitivity to nutlin-3 than B-CLL cells and no synergism with the genotoxic drugs [6].
  • In vitro treatment with nutlin-3 induced a significant cytotoxicity on primary CD19(+) B-CLL cells, but not on normal CD19(+) B lymphocytes, peripheral-blood mononuclear cells, or bone marrow hematopoietic progenitors [2].
  • Significantly, given the importance of the bone marrow microenvironment for the support and drug resistance of myeloma cells, tumor cells undergo effective apoptosis also in the presence of stromal cells, which themselves appear to tolerate exposure to nutlin-3 [1].

Biological context of Nutlin-3

  • Importantly, we found that the ECT2 gene is bound by p53 in vivo in response to DNA damage and Nutlin-3 treatment [7].
  • This is due to a p53-mediated down-regulation of SDF-1 mRNA, which can be exacerbated on activation of p53 by the drug Nutlin-3 [8].
  • Although HdmX overexpression yielded cells resistant to Nutlin-3, ablation of HdmX expression by short hairpin RNA sensitized tumor cells to Nutlin-3-mediated cell death or arrest [9].
  • Remarkably, surviving SK-N-SH cells adopted a senescence-like phenotype, whereas CLB-GA and NGP cells underwent neuronal differentiation. p53 dependence of these alternative outcomes of nutlin-3 treatment was evidenced by abrogation of the effects when p53 was knocked down by lentiviral-mediated short hairpin RNA interference [10].
  • The cytoprotective effects of Nutlin-3 were not related to its regulation of p53 or consequent gene expression during cisplatin treatment [11].

Anatomical context of Nutlin-3


Associations of Nutlin-3 with other chemical compounds


Gene context of Nutlin-3


Analytical, diagnostic and therapeutic context of Nutlin-3


  1. Nongenotoxic activation of the p53 pathway as a therapeutic strategy for multiple myeloma. Stühmer, T., Chatterjee, M., Hildebrandt, M., Herrmann, P., Gollasch, H., Gerecke, C., Theurich, S., Cigliano, L., Manz, R.A., Daniel, P.T., Bommert, K., Vassilev, L.T., Bargou, R.C. Blood (2005) [Pubmed]
  2. Functional integrity of the p53-mediated apoptotic pathway induced by the nongenotoxic agent nutlin-3 in B-cell chronic lymphocytic leukemia (B-CLL). Secchiero, P., Barbarotto, E., Tiribelli, M., Zerbinati, C., di Iasio, M.G., Gonelli, A., Cavazzini, F., Campioni, D., Fanin, R., Cuneo, A., Zauli, G. Blood (2006) [Pubmed]
  3. Nutlin3 blocks vascular endothelial growth factor induction by preventing the interaction between hypoxia inducible factor 1alpha and Hdm2. LaRusch, G.A., Jackson, M.W., Dunbar, J.D., Warren, R.S., Donner, D.B., Mayo, L.D. Cancer Res. (2007) [Pubmed]
  4. (R)-roscovitine (CYC202, Seliciclib) sensitizes SH-SY5Y neuroblastoma cells to nutlin-3-induced apoptosis. Ribas, J., Boix, J., Meijer, L. Exp. Cell Res. (2006) [Pubmed]
  5. Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy. Tovar, C., Rosinski, J., Filipovic, Z., Higgins, B., Kolinsky, K., Hilton, H., Zhao, X., Vu, B.T., Qing, W., Packman, K., Myklebost, O., Heimbrook, D.C., Vassilev, L.T. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  6. MDM2 antagonists activate p53 and synergize with genotoxic drugs in B-cell chronic lymphocytic leukemia cells. Coll-Mulet, L., Iglesias-Serret, D., Santidrián, A.F., Cosialls, A.M., de Frias, M., Castaño, E., Campàs, C., Barragán, M., de Sevilla, A.F., Domingo, A., Vassilev, L.T., Pons, G., Gil, J. Blood (2006) [Pubmed]
  7. The epithelial cell transforming sequence 2, a guanine nucleotide exchange factor for Rho GTPases, is repressed by p53 via protein methyltransferases and is required for G1-S transition. Scoumanne, A., Chen, X. Cancer Res. (2006) [Pubmed]
  8. p53 Attenuates Cancer Cell Migration and Invasion through Repression of SDF-1/CXCL12 Expression in Stromal Fibroblasts. Moskovits, N., Kalinkovich, A., Bar, J., Lapidot, T., Oren, M. Cancer Res. (2006) [Pubmed]
  9. Levels of HdmX expression dictate the sensitivity of normal and transformed cells to Nutlin-3. Patton, J.T., Mayo, L.D., Singhi, A.D., Gudkov, A.V., Stark, G.R., Jackson, M.W. Cancer Res. (2006) [Pubmed]
  10. Small-Molecule MDM2 Antagonists as a New Therapy Concept for Neuroblastoma. Van Maerken, T., Speleman, F., Vermeulen, J., Lambertz, I., De Clercq, S., De Smet, E., Yigit, N., Coppens, V., Philipp??, J., De Paepe, A., Marine, J.C., Vandesompele, J. Cancer Res. (2006) [Pubmed]
  11. Nutlin-3 Protects Kidney Cells during Cisplatin Therapy by Suppressing Bax/Bak Activation. Jiang, M., Pabla, N., Murphy, R.F., Yang, T., Yin, X.M., Degenhardt, K., White, E., Dong, Z. J. Biol. Chem. (2007) [Pubmed]
  12. Circumvention and reactivation of the p53 oncogene checkpoint in mouse colon tumors. Aizu, W., Belinsky, G.S., Flynn, C., Noonan, E.J., Boes, C.C., Godman, C.A., Doshi, B., Nambiar, P.R., Rosenberg, D.W., Giardina, C. Biochem. Pharmacol. (2006) [Pubmed]
  13. Antiangiogenic activity of the MDM2 antagonist nutlin-3. Secchiero, P., Corallini, F., Gonelli, A., Dell'Eva, R., Vitale, M., Capitani, S., Albini, A., Zauli, G. Circ. Res. (2007) [Pubmed]
  14. Phosphorylation of p53 on key serines is dispensable for transcriptional activation and apoptosis. Thompson, T., Tovar, C., Yang, H., Carvajal, D., Vu, B.T., Xu, Q., Wahl, G.M., Heimbrook, D.C., Vassilev, L.T. J. Biol. Chem. (2004) [Pubmed]
  15. MDM2 antagonist nutlin-3 displays antiproliferative and proapoptotic activity in mantle cell lymphoma. Tabe, Y., Sebasigari, D., Jin, L., Rudelius, M., Davies-Hill, T., Miyake, K., Miida, T., Pittaluga, S., Raffeld, M. Clin. Cancer Res. (2009) [Pubmed]
  16. Restoration of p53 pathway by nutlin-3 induces cell cycle arrest and apoptosis in human rhabdomyosarcoma cells. Miyachi, M., Kakazu, N., Yagyu, S., Katsumi, Y., Tsubai-Shimizu, S., Kikuchi, K., Tsuchiya, K., Iehara, T., Hosoi, H. Clin. Cancer Res. (2009) [Pubmed]
  17. An Organometallic Protein Kinase Inhibitor Pharmacologically Activates p53 and Induces Apoptosis in Human Melanoma Cells. Smalley, K.S., Contractor, R., Haass, N.K., Kulp, A.N., Atilla-Gokcumen, G.E., Williams, D.S., Bregman, H., Flaherty, K.T., Soengas, M.S., Meggers, E., Herlyn, M. Cancer Res. (2007) [Pubmed]
  18. An shRNA barcode screen provides insight into cancer cell vulnerability to MDM2 inhibitors. Brummelkamp, T.R., Fabius, A.W., Mullenders, J., Madiredjo, M., Velds, A., Kerkhoven, R.M., Bernards, R., Beijersbergen, R.L. Nat. Chem. Biol. (2006) [Pubmed]
WikiGenes - Universities