Antineoplastic Agents. 604. the Path of Quinstatin Derivatives to Antibody Drug Conjugates

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1 Citation (Scopus)

Abstract

To further evaluate the exceptional cancer cell growth inhibition by the quinstatins, of which one of the series, quinstatin 8, approaches the exceptional cytotoxic activity of the parent dolastatin 10 (1), four of the quinstatins have been converted to desmethyl derivatives. Three of the four (4, 5, and 8 [7b-d]) were next bonded to the linker (8) employed in the synthesis of the very successful and structurally related anticancer drug Adcetris (3). Owing to these structural modifications, a next step could be taken by bonding to a monoclonal antibody, thereby producing an antibody drug conjugate (ADC) related to Adcetris structurally but with the possibility of a wider spectrum of activity and utility.

Original languageEnglish (US)
Pages (from-to)2447-2452
Number of pages6
JournalJournal of Natural Products
Volume80
Issue number9
DOIs
StatePublished - Jan 1 2017

Fingerprint

dolastatin 10
Antineoplastic Agents
Derivatives
Antibodies
Cell growth
Pharmaceutical Preparations
Monoclonal Antibodies
Growth
Neoplasms
cAC10-vcMMAE
dolastatin 1

ASJC Scopus subject areas

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

Cite this

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title = "Antineoplastic Agents. 604. the Path of Quinstatin Derivatives to Antibody Drug Conjugates",
abstract = "To further evaluate the exceptional cancer cell growth inhibition by the quinstatins, of which one of the series, quinstatin 8, approaches the exceptional cytotoxic activity of the parent dolastatin 10 (1), four of the quinstatins have been converted to desmethyl derivatives. Three of the four (4, 5, and 8 [7b-d]) were next bonded to the linker (8) employed in the synthesis of the very successful and structurally related anticancer drug Adcetris (3). Owing to these structural modifications, a next step could be taken by bonding to a monoclonal antibody, thereby producing an antibody drug conjugate (ADC) related to Adcetris structurally but with the possibility of a wider spectrum of activity and utility.",
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AB - To further evaluate the exceptional cancer cell growth inhibition by the quinstatins, of which one of the series, quinstatin 8, approaches the exceptional cytotoxic activity of the parent dolastatin 10 (1), four of the quinstatins have been converted to desmethyl derivatives. Three of the four (4, 5, and 8 [7b-d]) were next bonded to the linker (8) employed in the synthesis of the very successful and structurally related anticancer drug Adcetris (3). Owing to these structural modifications, a next step could be taken by bonding to a monoclonal antibody, thereby producing an antibody drug conjugate (ADC) related to Adcetris structurally but with the possibility of a wider spectrum of activity and utility.

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