Related Experiment Video

Updated: Jun 10, 2026

Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor
07:21

Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor

Published on: May 2, 2022

Motesanib inhibits Kit mutations associated with gastrointestinal stromal tumors

Sean Caenepeel1, Lisa Renshaw-Gegg, Angelo Baher

  • 1Department of Oncology Research, Amgen Inc,, One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA.

Journal of Experimental & Clinical Cancer Research : CR
|July 17, 2010
PubMed
Abstract

Insights

Motesanib effectively inhibits primary activating mutations and some imatinib-resistant secondary mutations in Kit, a key driver in gastrointestinal stromal tumors (GIST). This suggests potential for motesanib in treating GIST with specific Kit alterations.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Activating mutations in Kit receptor tyrosine kinase are crucial in gastrointestinal stromal tumor (GIST) pathogenesis.
  • Platelet-derived growth factor receptor (PDGFR) also plays a role in GIST development.

Purpose of the Study:

  • To investigate the activity of motesanib against primary activating Kit mutants.
  • To evaluate motesanib's efficacy against Kit mutants associated with secondary resistance to imatinib.

Main Methods:

  • Motesanib's inhibitory activity was tested against various single- and double-mutant Kit isoforms.
  • Assays included autophosphorylation inhibition and Ba/F3 cell proliferation assays.

Main Results:

  • Motesanib inhibited primary activating Kit mutations in exon 9 and exon 11 with low IC50 values.
  • The drug showed activity against some imatinib-resistant Kit mutants but not the D816V mutant.

Conclusions:

  • Motesanib demonstrates inhibitory activity against primary Kit mutations.
  • The findings suggest motesanib's potential utility against certain imatinib-resistant secondary Kit mutations in GIST.

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