@article{fcb2144001d44954832d44f76ef3ee12,
title = "Isolation of dolastatins 10-15 from the marine mollusc dolabella auricularia",
abstract = "A twenty year pursuit of the cell growth inhibitory and antineoplastic constituents of the Western Indian Ocean (Mauritius) sea hare Dolabella auricularia has resulted in the discovery of fifteen structurally unique peptide, cyclopeptide, depsipeptide, and cyclodepsipeptide type-substances designated dolastatins 1-15. Solution of the difficult isolation problems leading to discovery of dolastatins 10-15 in 10-6 to 10-7% yields required 1,600 kg of Dolabella aurlcularia. To date, this represents the largest scale separation of sea hare components. Of these dolastatin 10 (4) has displayed unprecedented potency in experimental antineoplastic and tubulin assembly systems. Dolastatin 15 (9), and to a lesser extent dolastatin 14 (8) were also found to exhibit unusually strong antineoplastic activity. Both dolastatina 10 and 15 are in advanced preclinical development. Details of the isolation strategies and structural summaries for dolastatins 10-15 have been recorded. Intensive Study of the cell growth inhibition and antineoplastic constituents of the sea hare Dolabella auricularia provided the structurally unique peptides designated dolastatins 1-15.",
author = "George Pettit and Yoshiaki Kamano and Herald, {Cherry L.} and Youichi Fujii and Haruhisa Kizu and Boyd, {Michael R.} and Boettner, {Fred E.} and Doubek, {Dennis L.} and Schmidt, {Jean M.} and Jean Chapuis and Claude Michel",
note = "Funding Information: The remarkable potency of dolastatin 10 against the preceding broad selection of human cancer cell lines combined with its extraordinary activity against various in vivo experimental cancer systems has allowed it to be selected for preclinical development by the NCI. For analogous reasons dolastatin 15 is also undergoing preclinical investigations. Both dolastatins 10 and 15 are scheduled to enter phase I clinical trial in 1993. ACKNOWLFXMNTS With pleasure we thank, for financial support, Outstanding Investigator Grant CA-44344-OlAl-04 and PHS Grant CA-16049-01-12 awarded by the Division of Cancer Treatment NCI, DHHS, The Fannie E. Rippel Foundation, the Robert B. Dalton Endowment,E leanor W. Libby, the Waddell Foundation (Donald Ware), Virginia Piper, Jack W. Whiteman, the Arizona Disease Control Research Commission, Herbert K. and Diane Curmaings( The Nathen Crumings Foundation, Inc.), Polly J. Trautman, and Lotte Flugel. For other assistance we thank Drs. N. I. Suffness, J. D. Douros, J. L. Hartwell, R. Shoemaker, K. Kitahara, R. H. Ode, F. Ferrari, L. W. Knapp, G. Hendler, H. Bertsch, and Ms. B. J. Abbott, S. Kamano, S. O'Connor, H. Duplissa and K. Welch, Messrs. P. L. Daschner, L. Williams, J. F. Day, G. C. Bryan, D. Vanell, S. Morris, and C. Ochoa. NSF Grant CHE-8409644a nd the NSF Regional Instrumentation Facility inNebraska (Grant CHF.-8620177).",
year = "1993",
doi = "10.1016/0040-4020(93)80003-C",
language = "English (US)",
volume = "49",
pages = "9151--9170",
journal = "Tetrahedron",
issn = "0040-4020",
publisher = "Elsevier Limited",
number = "41",
}