Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

Targeting cell surface alpha(v)beta(3) integrin increases therapeutic efficacies of a legumain protease-activated auristatin prodrug

Academic Article
uri icon
  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Liu, Y.
  • Bajjuri, K. M.
  • Liu, C.
  • Sinha, Subhash

publication date

  • January 2012

journal

  • Molecular Pharmaceutics  Journal

abstract

  • Novel monomethylauristatin E (MMAE) prodrug 8 was designed and prepared that bound cell surface glycoprotein integrin αvβ3, and was activated using legumain protease as a catalyst. Upon activation, prodrug 8 strongly induced the death of MDA-MB-435 cells that express integrin αvβ3 on cell surface. Efficacies of prodrug 8 were also determined in vivo using animal models of 4T1 murine breast cancer, D121 Lewis lung carcinoma, and MDA-MB-435 human breast cancer. The results demonstrated that prodrug 8 decreased tumor growth and metastasis effectively. In comparison to the parent cytotoxin, MMAE, and prodrug 3, prodrug 8 was less toxic to mouse white blood cells. The latter caused no loss in weight gain of mice at a dose 3 mg/kg, which is over 30 times in excess to MMAE (0.1 mg/kg). We hypothesize that overexpression and colocalization of integrin αvβ3 and legumain protease on tumor cells, tumor vasculature, and/or tumor microenvironments can be exploited to enhance the efficacy and selectivity of potent cytotoxins, such as MMAE, which is otherwise too toxic to use for therapy.

subject areas

  • Animals
  • Antineoplastic Agents
  • Biotransformation
  • Cell Line, Tumor
  • Cell Survival
  • Cysteine Endopeptidases
  • Drug Design
  • Humans
  • Integrin alphaVbeta3
  • Lung Neoplasms
  • Maximum Tolerated Dose
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Nude
  • Neoplasm Proteins
  • Neoplasms, Experimental
  • Oligopeptides
  • Prodrugs
  • Rats
  • Survival Analysis
scroll to property group menus

Research

keywords

  • integrin
  • legumain
  • monomethylauristatin E (MMAE)
  • prodrug
  • prodrug activation
scroll to property group menus

Identity

PubMed Central ID

  • PMC3277864

International Standard Serial Number (ISSN)

  • 1543-8384

Digital Object Identifier (DOI)

  • 10.1021/mp200434n

PubMed ID

  • 22044266
scroll to property group menus

Additional Document Info

start page

  • 168

end page

  • 175

volume

  • 9

issue

  • 1

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support