Isolation and structural elucidation of the cytostatic linear depsipeptide dolastatin 15

• US 4,879,278 A
• Filed: 05/16/1989
• Issued: 11/07/1989
• Est. Priority Date: 05/16/1989
• Status: Expired due to Term

• Current Assignee: Arizona Board of Regents (University of Arizona)
• Original Assignee: Arizona Board of Regents (University of Arizona)
• Inventors: Pettit, George R., Kamano, Yoshiaki
• Primary Examiner(s): LEE, LESTER
• Application Number:
  US07/352,851
• Time in Patent Office: 175 Days
• Field of Search: 530/329, 530/330, 514/16, 514/17, 514/21
• US Class Current: 514/19.2
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: C07K 11/00 Depsipeptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof

Abstract

A new cytostatic depsipeptide, designated "dolastatin 15", was isolated from the Indian Ocean shell-like mollusk Dolabella auricularia. Dolastatin 15 inhibited growth of the PS leukemia with ED₅₀ 0.0024 μg/mL. Pharmaceutical preparations and therapeutic regimens utilizing Dolastatin 15, its synthetic counterpart and pharmaceutically active derivatives are disclosed. Dolastatin 15 has the structural formula: ##STR1##

Claims

1. A cell growth inhibitory substance denominated dolastatin 15 and having the structural formula:

##STR4##

2. A pharmaceutical preparation comprising a pharmaceutically acceptable carrier and an effective amount of a natural or synthetic substance or a non-toxic pharmaceutically active derivative thereof, said substance having the structural formula:

##STR5##

3. A method of treating a host afflicted with neoplastic disease comprising administering to said host an effective amount of a natural or synthetic substance or a pharmaceutically active non-toxic derivative thereof and a pharmaceutically acceptable carrier, said substance having the structural formula:

##STR6##

4. A method according to claim 3 in which said substance is administered intravenously, at a dosage level of from 0.1 up to about 20 mg per kilogram of host body weight.

5. A method according to claim 3 in which said substance is administered subcutaneously, at a dosage level of from 1 up to about 50 mg per kilogram of host body weight.

6. A method according to claim 3 in which said substance is administered orally, at a dosage level of from 5 up to about 100 mg per kilogram of host body weight.

7. A method according to claim 3 in which said neoplastic disease is lymphocytic leukemia P388.

8. A method according to claim 7 in which said small but effective amount comprises from about 1 up to about 4 g per kilogram of host body weight.