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Chemical Compound Review

Dolastatin 10     2-[(2-dimethylamino-3- methyl...

Synonyms: AGN-PC-00PTZ8, SureCN13840941, Neuro_000215, AC1L2OAS, NSC376128, ...
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Disease relevance of C11280


High impact information on C11280


Chemical compound and disease context of C11280


Biological context of C11280

  • Modeling studies revealed a highly favored binding site for dolastatin 10 at the + end of beta-tubulin in proximity to the exchangeable site GDP [12].
  • A tripeptide segment of dolastatin 10 also effectively inhibits tubulin polymerization and GTP hydrolysis [13].
  • Agents were added to triplicate wells, and cell count, viability, mitosis, and apoptosis were assessed after 24 h of incubation at 37 degrees C. Results showed that dolastatin 10 had no apparent inhibition of cell growth at concentrations less than 500 pg/ml [14].
  • In initial experiments with 5 microM tubulin and 5 microM vinblastine, spongistatin 1 and dolastatin 10 both had IC50 values of 2 microM, whereas halichondrin B had an IC50 value of 5 microM [15].
  • Dolastatin 10 is an unusual peptide of marine origin which binds to tubulin in the vinblastine/maytansine/phomopsin-binding region and potently inhibits mitosis [16].

Anatomical context of C11280


Associations of C11280 with other chemical compounds


Gene context of C11280

  • Role of P-glycoprotein in dolastatin 10 resistance [26].
  • While these findings suggested the involvement of the P-glycoprotein (P-gp) in dolastatin 10 resistance, we performed similar studies in a CHO cell line transfected with the human mdr1 cDNA [26].
  • CONCLUSIONS: These findings suggest that dolastatin 10 has potent activity against SCLC and that the modulation of apoptotic pathways deserves further evaluation as an anticancer strategy [27].
  • However, upon treatment of cells with a combination of bryostatin 1 and dolastatin 10 or auristatin PE, the induction of cIAP-1 was abolished, leading to a significant increase in apoptosis [28].
  • WSU-DLCL2 cells were negative for p53 protein expression, upon treatment with Bryo1 or Dol10, the expression of p53 was weak and moderate with the Bryo1/Dol10 combination [29].

Analytical, diagnostic and therapeutic context of C11280


  1. Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Doronina, S.O., Toki, B.E., Torgov, M.Y., Mendelsohn, B.A., Cerveny, C.G., Chace, D.F., DeBlanc, R.L., Gearing, R.P., Bovee, T.D., Siegall, C.B., Francisco, J.A., Wahl, A.F., Meyer, D.L., Senter, P.D. Nat. Biotechnol. (2003) [Pubmed]
  2. Phase II study of dolastatin-10 in patients with hormone-refractory metastatic prostate adenocarcinoma. Vaishampayan, U., Glode, M., Du, W., Kraft, A., Hudes, G., Wright, J., Hussain, M. Clin. Cancer Res. (2000) [Pubmed]
  3. Sustained intracellular retention of dolastatin 10 causes its potent antimitotic activity. Verdier-Pinard, P., Kepler, J.A., Pettit, G.R., Hamel, E. Mol. Pharmacol. (2000) [Pubmed]
  4. The molecular pharmacology of symplostatin 1: a new antimitotic dolastatin 10 analog. Mooberry, S.L., Leal, R.M., Tinley, T.L., Luesch, H., Moore, R.E., Corbett, T.H. Int. J. Cancer (2003) [Pubmed]
  5. Dolastatin-10 in metastatic melanoma: a phase II and pharmokinetic trial of the California Cancer Consortium. Margolin, K., Longmate, J., Synold, T.W., Gandara, D.R., Weber, J., Gonzalez, R., Johansen, M.J., Newman, R., Baratta, T., Doroshow, J.H. Investigational new drugs. (2001) [Pubmed]
  6. Growth inhibition of human lymphoma cell lines by the marine products, dolastatins 10 and 15. Beckwith, M., Urba, W.J., Longo, D.L. J. Natl. Cancer Inst. (1993) [Pubmed]
  7. Antineoplastic dolastatins: potent inhibitors of hematopoietic progenitor cells. Jacobsen, S.E., Ruscetti, F.W., Longo, D.L., Keller, J.R. J. Natl. Cancer Inst. (1991) [Pubmed]
  8. Serine-70 is one of the critical sites for drug-induced Bcl2 phosphorylation in cancer cells. Haldar, S., Basu, A., Croce, C.M. Cancer Res. (1998) [Pubmed]
  9. Characterization of the interaction of cryptophycin 1 with tubulin: binding in the Vinca domain, competitive inhibition of dolastatin 10 binding, and an unusual aggregation reaction. Bai, R., Schwartz, R.E., Kepler, J.A., Pettit, G.R., Hamel, E. Cancer Res. (1996) [Pubmed]
  10. Antitumour evaluation of dolastatins 10 and 15 and their measurement in plasma by radioimmunoassay. Aherne, G.W., Hardcastle, A., Valenti, M., Bryant, A., Rogers, P., Pettit, G.R., Srirangam, J.K., Kelland, L.R. Cancer Chemother. Pharmacol. (1996) [Pubmed]
  11. Synergistic interaction of selected marine animal anticancer drugs against human diffuse large cell lymphoma. Mohammad, R.M., Pettit, G.R., Almatchy, V.P., Wall, N., Varterasian, M., Al-Katib, A. Anticancer Drugs (1998) [Pubmed]
  12. Direct photoaffinity labeling by dolastatin 10 of the amino-terminal peptide of beta-tubulin containing cysteine 12. Bai, R., Covell, D.G., Taylor, G.F., Kepler, J.A., Copeland, T.D., Nguyen, N.Y., Pettit, G.R., Hamel, E. J. Biol. Chem. (2004) [Pubmed]
  13. Binding of dolastatin 10 to tubulin at a distinct site for peptide antimitotic agents near the exchangeable nucleotide and vinca alkaloid sites. Bai, R.L., Pettit, G.R., Hamel, E. J. Biol. Chem. (1990) [Pubmed]
  14. Successful treatment of human chronic lymphocytic leukemia xenografts with combination biological agents auristatin PE and bryostatin 1. Mohammad, R.M., Varterasian, M.L., Almatchy, V.P., Hannoudi, G.N., Pettit, G.R., Al-Katib, A. Clin. Cancer Res. (1998) [Pubmed]
  15. Spongistatin 1, a highly cytotoxic, sponge-derived, marine natural product that inhibits mitosis, microtubule assembly, and the binding of vinblastine to tubulin. Bai, R., Cichacz, Z.A., Herald, C.L., Pettit, G.R., Hamel, E. Mol. Pharmacol. (1993) [Pubmed]
  16. Interaction of dolastatin 10 with bovine brain tubulin. Ludueña, R.F., Roach, M.C., Prasad, V., Pettit, G.R. Biochem. Pharmacol. (1992) [Pubmed]
  17. Phase I and pharmacokinetic study of TZT-1027, a novel synthetic dolastatin 10 derivative, administered as a 1-hour intravenous infusion every 3 weeks in patients with advanced refractory cancer. Schöffski, P., Thate, B., Beutel, G., Bolte, O., Otto, D., Hofmann, M., Ganser, A., Jenner, A., Cheverton, P., Wanders, J., Oguma, T., Atsumi, R., Satomi, M. Ann. Oncol. (2004) [Pubmed]
  18. Dolastatin 15, a potent antimitotic depsipeptide derived from Dolabella auricularia. Interaction with tubulin and effects of cellular microtubules. Bai, R., Friedman, S.J., Pettit, G.R., Hamel, E. Biochem. Pharmacol. (1992) [Pubmed]
  19. Novel therapeutic agents for the treatment of myelodysplastic syndromes. Cheson, B.D., Zwiebel, J.A., Dancey, J., Murgo, A. Semin. Oncol. (2000) [Pubmed]
  20. Preclinical pharmacology of the natural marine product dolastatin 10 (NSC 376128). Newman, R.A., Fuentes, A., Covey, J.M., Benvenuto, J.A. Drug Metab. Dispos. (1994) [Pubmed]
  21. Two photoaffinity analogues of the tripeptide, hemiasterlin, exclusively label alpha-tubulin. Nunes, M., Kaplan, J., Wooters, J., Hari, M., Minnick, A.A., May, M.K., Shi, C., Musto, S., Beyer, C., Krishnamurthy, G., Qiu, Y., Loganzo, F., Ayral-Kaloustian, S., Zask, A., Greenberger, L.M. Biochemistry (2005) [Pubmed]
  22. A new tubulin polymerization inhibitor, auristatin PE, induces tumor regression in a human Waldenstrom's macroglobulinemia xenograft model. Mohammad, R.M., Limvarapuss, C., Wall, N.R., Hamdy, N., Beck, F.W., Pettit, G.R., Al-Katib, A. Int. J. Oncol. (1999) [Pubmed]
  23. Isolation of dolastatin 10 from the marine cyanobacterium Symploca species VP642 and total stereochemistry and biological evaluation of its analogue symplostatin 1. Luesch, H., Moore, R.E., Paul, V.J., Mooberry, S.L., Corbett, T.H. J. Nat. Prod. (2001) [Pubmed]
  24. Antitumor activity of TZT-1027 (Soblidotin). Watanabe, J., Minami, M., Kobayashi, M. Anticancer Res. (2006) [Pubmed]
  25. Antineoplastic agents. 515. Synthesis of human cancer cell growth inhibitors derived from 3,4-methylenedioxy-5,4'-dimethoxy-3'-amino-Z-stilbene. Pettit, G.R., Anderson, C.R., Gapud, E.J., Jung, M.K., Knight, J.C., Hamel, E., Pettit, R.K. J. Nat. Prod. (2005) [Pubmed]
  26. Role of P-glycoprotein in dolastatin 10 resistance. Toppmeyer, D.L., Slapak, C.A., Croop, J., Kufe, D.W. Biochem. Pharmacol. (1994) [Pubmed]
  27. Activity of dolastatin 10 against small-cell lung cancer in vitro and in vivo: induction of apoptosis and bcl-2 modification. Kalemkerian, G.P., Ou, X., Adil, M.R., Rosati, R., Khoulani, M.M., Madan, S.K., Pettit, G.R. Cancer Chemother. Pharmacol. (1999) [Pubmed]
  28. Modulation of cIAP-1 by novel antitubulin agents when combined with bryostatin 1 results in increased apoptosis in the human early pre-B acute lymphoblastic leukemia cell line Reh. Wall, N.R., Mohammad, R.M., Nabha, S.M., Pettit, G.R., Al-Katib, A.M. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  29. The bcl-2 and p53 oncoproteins can be modulated by bryostatin 1 and dolastatins in human diffuse large cell lymphoma. Maki, A., Diwakaran, H., Redman, B., al-Asfar, S., Pettit, G.R., Mohammad, R.M., al-Katib, A. Anticancer Drugs (1995) [Pubmed]
  30. Interaction of dolastatin 10 with tubulin: induction of aggregation and binding and dissociation reactions. Bai, R., Taylor, G.F., Schmidt, J.M., Williams, M.D., Kepler, J.A., Pettit, G.R., Hamel, E. Mol. Pharmacol. (1995) [Pubmed]
  31. Specific activities of dolastatin 10 and peptide derivatives against Cryptococcus neoformans. Pettit, R.K., Pettit, G.R., Hazen, K.C. Antimicrob. Agents Chemother. (1998) [Pubmed]
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