Antineoplastic Agents. 603. Quinstatins

Exceptional Cancer Cell Growth Inhibitors

Research output: Contribution to journalReview article

7 Citations (Scopus)

Abstract

Discovery of the exceptionally powerful anticancer drug dolastatin 10 (1), contained in the sea hare Dolabella auricularia, opened a new frontier needed for improving human cancer treatment. Subsequently, major advances have been achieved based on results of structurally modifying this unusual natural peptide while maintaining the remarkable anticancer activity necessary for preparation of successful monoclonal antibody drug conjugates (ADC). Among the first several hundred SAR products based on dolastatin 10 our group synthesized and termed auristatins was auristatin E (2a). An anticancer activity-equivalent, desmethylaurisatin E (2b), linked to a CD30 monoclonal antibody is the very successful anticancer drug Adcetris, now approved for use in 65 countries. In the present investigation, we discovered a new subset of auristatins designated quinstatins derived from dolastatin 10 by replacing the C-terminal Doe unit with a carefully designed quinoline, which led to low or subnanomolar levels of cancer cell growth inhibition required for construction of chemically unique ADC drugs. The synthesis of quinstatins 2-8 is presented along with their cancer cell line biological data.

Original languageEnglish (US)
Pages (from-to)692-698
Number of pages7
JournalJournal of Natural Products
Volume80
Issue number3
DOIs
StatePublished - Mar 24 2017

Fingerprint

dolastatin 10
Growth Inhibitors
Antineoplastic Agents
Pharmaceutical Preparations
Neoplasms
Monoclonal Antibodies
Hares
Oncology
Cell growth
Oceans and Seas
Cells
Cell Line
Peptides
Antibodies
Growth
auristatin

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

Cite this

Antineoplastic Agents. 603. Quinstatins : Exceptional Cancer Cell Growth Inhibitors. / Pettit, George; Melody, Noeleen; Chapuis, Jean.

In: Journal of Natural Products, Vol. 80, No. 3, 24.03.2017, p. 692-698.

Research output: Contribution to journalReview article

@article{adb5db366cf34fc7a48c3ad3df61a104,
title = "Antineoplastic Agents. 603. Quinstatins: Exceptional Cancer Cell Growth Inhibitors",
abstract = "Discovery of the exceptionally powerful anticancer drug dolastatin 10 (1), contained in the sea hare Dolabella auricularia, opened a new frontier needed for improving human cancer treatment. Subsequently, major advances have been achieved based on results of structurally modifying this unusual natural peptide while maintaining the remarkable anticancer activity necessary for preparation of successful monoclonal antibody drug conjugates (ADC). Among the first several hundred SAR products based on dolastatin 10 our group synthesized and termed auristatins was auristatin E (2a). An anticancer activity-equivalent, desmethylaurisatin E (2b), linked to a CD30 monoclonal antibody is the very successful anticancer drug Adcetris, now approved for use in 65 countries. In the present investigation, we discovered a new subset of auristatins designated quinstatins derived from dolastatin 10 by replacing the C-terminal Doe unit with a carefully designed quinoline, which led to low or subnanomolar levels of cancer cell growth inhibition required for construction of chemically unique ADC drugs. The synthesis of quinstatins 2-8 is presented along with their cancer cell line biological data.",
author = "George Pettit and Noeleen Melody and Jean Chapuis",
year = "2017",
month = "3",
day = "24",
doi = "10.1021/acs.jnatprod.6b01006",
language = "English (US)",
volume = "80",
pages = "692--698",
journal = "Journal of Natural Products",
issn = "0163-3864",
publisher = "American Chemical Society",
number = "3",

}

TY - JOUR

T1 - Antineoplastic Agents. 603. Quinstatins

T2 - Exceptional Cancer Cell Growth Inhibitors

AU - Pettit, George

AU - Melody, Noeleen

AU - Chapuis, Jean

PY - 2017/3/24

Y1 - 2017/3/24

N2 - Discovery of the exceptionally powerful anticancer drug dolastatin 10 (1), contained in the sea hare Dolabella auricularia, opened a new frontier needed for improving human cancer treatment. Subsequently, major advances have been achieved based on results of structurally modifying this unusual natural peptide while maintaining the remarkable anticancer activity necessary for preparation of successful monoclonal antibody drug conjugates (ADC). Among the first several hundred SAR products based on dolastatin 10 our group synthesized and termed auristatins was auristatin E (2a). An anticancer activity-equivalent, desmethylaurisatin E (2b), linked to a CD30 monoclonal antibody is the very successful anticancer drug Adcetris, now approved for use in 65 countries. In the present investigation, we discovered a new subset of auristatins designated quinstatins derived from dolastatin 10 by replacing the C-terminal Doe unit with a carefully designed quinoline, which led to low or subnanomolar levels of cancer cell growth inhibition required for construction of chemically unique ADC drugs. The synthesis of quinstatins 2-8 is presented along with their cancer cell line biological data.

AB - Discovery of the exceptionally powerful anticancer drug dolastatin 10 (1), contained in the sea hare Dolabella auricularia, opened a new frontier needed for improving human cancer treatment. Subsequently, major advances have been achieved based on results of structurally modifying this unusual natural peptide while maintaining the remarkable anticancer activity necessary for preparation of successful monoclonal antibody drug conjugates (ADC). Among the first several hundred SAR products based on dolastatin 10 our group synthesized and termed auristatins was auristatin E (2a). An anticancer activity-equivalent, desmethylaurisatin E (2b), linked to a CD30 monoclonal antibody is the very successful anticancer drug Adcetris, now approved for use in 65 countries. In the present investigation, we discovered a new subset of auristatins designated quinstatins derived from dolastatin 10 by replacing the C-terminal Doe unit with a carefully designed quinoline, which led to low or subnanomolar levels of cancer cell growth inhibition required for construction of chemically unique ADC drugs. The synthesis of quinstatins 2-8 is presented along with their cancer cell line biological data.

UR - http://www.scopus.com/inward/record.url?scp=85016162468&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016162468&partnerID=8YFLogxK

U2 - 10.1021/acs.jnatprod.6b01006

DO - 10.1021/acs.jnatprod.6b01006

M3 - Review article

VL - 80

SP - 692

EP - 698

JO - Journal of Natural Products

JF - Journal of Natural Products

SN - 0163-3864

IS - 3

ER -