Licensing status

Publication and contact information


Gastrointestinal cancer

Stem cell factor receptor tyrosine kinase (c-Kit; KIT; CD117)

In vitro studies suggest quinazoline-pyrazolourea-based KIT inhibitors could help treat Gleevec imatinib-resistant gastrointestinal stromal tumors (GISTs). Chemical synthesis, SAR and in vitro testing identified quinazoline-pyrazolourea analogs that inhibited wild-type KIT and two imatinib-resistant KIT mutants with low nanomolar IC50 values. In human GIST cell lines expressing constitutively active KIT or the imatinib-resistant T670I KIT mutant, 3 of the lead compounds caused 50% growth inhibition at low nanomolar concentrations. Future studies could include testing the lead compounds in animal models bearing imatinib-resistant GIST xenografts.
Novartis AG markets Gleevec, a BCR-ABL tyrosine kinase inhibitor, to treat GISTs, acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML) and other hematological malignancies. The drug also is under review for hypertension and in Phase II testing to treat melanoma and scleroderma.
AB Science S.A.'s KIT inhibitor masitinib is under review for imatinib-resistant GISTs and in Phase III testing to treat other cancers.

SciBX 6(28); doi:10.1038/scibx.2013.716
Published online July 25, 2013

Patent and licensing status unavailable

Richters, A. et al. J. Med. Chem.;
published online June 17, 2013;
Contact: Daniel Rauh, Technical University of Dortmund, Dortmund, Germany
Contact: Sebastian Bauer, University of Duisburg-Essen Medical School, Essen, Germany