BAY 43-9006 inhibition of oncogenic RET mutants

Journal of the National Cancer Institute
Francesca CarlomagnoMassimo Santoro

Abstract

Medullary and papillary thyroid carcinomas are often associated with oncogenic activation of the RET tyrosine kinase. We evaluated whether the biaryl urea BAY 43-9006, which is known to inhibit several other tyrosine kinases, blocks RET kinase function and oncogenic activity. We examined BAY 43-9006 activity against oncogenic RET in vitro and in cellular RET signaling in oncogenic RET-transfected NIH3T3 fibroblasts by using immunocomplex kinase assays and immunoblotting with phospho-specific antibodies. The effects of BAY 43-9006 on proliferation of human TPC1 and TT thyroid carcinoma cells, which harbor spontaneous oncogenic RET alleles, and on RAT1 fibroblasts transformed with oncogenic RET mutants, including mutants that are resistant to other chemotherapeutic agents, were determined using growth curves and flow cytometry. Growth of TT cell-derived xenograft tumors in athymic mice treated orally with BAY 43-9006 or with vehicle was measured. All statistical tests were two-sided. BAY 43-9006 inhibited oncogenic RET kinase activity at half-maximal inhibitory concentrations (IC50s) of 50 nM or less in NIH3T3 cells. It also arrested the growth of NIH3T3 and RAT1 fibroblasts transformed by oncogenic RET and of thyroid carcinoma c...Continue Reading

References

Apr 30, 1990·Biochemical and Biophysical Research Communications·Y IshizakaM Nagao
Feb 27, 1995·Biochemical and Biophysical Research Communications·F CarlomagnoA Fusco
Feb 19, 2000·Biochemical and Biophysical Research Communications·T IwashitaM Takahashi
May 29, 2000·Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association·D K BartschW Höppner
Sep 22, 2001·Endocrine-related Cancer·J F LyonsG Bollag
Jan 15, 2002·The Journal of Clinical Endocrinology and Metabolism·Fred H MenkoCornelis J M Lips
Apr 5, 2002·The Journal of Clinical Endocrinology and Metabolism·Francesca LombardoSebastiano Filetti
Feb 14, 2003·Lancet·Steven I Sherman
Apr 8, 2003·The Journal of Clinical Endocrinology and Metabolism·Francesca CarlomagnoMassimo Santoro
Jun 5, 2003·Cancer Cell·Sunil R Hingorani, David A Tuveson
Oct 17, 2003·The New England Journal of Medicine·Andreas MachensUNKNOWN European Multiple Endocrine Neoplasia (EUROMEN) Study Group
Oct 17, 2003·The New England Journal of Medicine·Gilbert J Cote, Robert F Gagel
Jul 9, 2004·Journal of the National Cancer Institute·Samuel A Wells, Joseph R Nevins
Jul 9, 2004·Journal of the National Cancer Institute·Giuditta CuccuruFranco Zunino
Aug 25, 2004·Cancer Cell·Michael W N Deininger, Brian J Druker
Aug 28, 2004·Endocrinology·Massimo SantoroAlfredo Fusco
Nov 19, 2004·Nature·Charles Sawyers
Dec 2, 2004·Nature Reviews. Drug Discovery·Henrik DaubAxel Ullrich
Feb 16, 2005·Cancer Cell·Ellen WeisbergJames D Griffin
Feb 25, 2005·The New England Journal of Medicine·Susumu KobayashiBalázs Halmos
May 3, 2005·Nature Reviews. Cancer·Stephen J Marx

❮ Previous
Next ❯

Citations

Jan 22, 2011·Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft·M KerntA Kampik
Jul 12, 2012·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Henrike WestekemperRalf A Hilger
May 17, 2011·Investigational New Drugs·Sylvie Négrier, Eric Raymond
Oct 19, 2011·Investigational New Drugs·Marilyne HorneckerMichel Tod
Oct 13, 2006·Pituitary·Yoshiki MurakumoMasahide Takahashi
Nov 12, 2009·Targeted Oncology·Jaume CapdevilaJosep Tabernero
Oct 6, 2007·Endocrine Pathology·Andrea Z LaiLois M Mulligan
Nov 15, 2012·Endocrine Pathology·Boban M ErovicOzgur Mete
Jan 30, 2013·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·M Majem, C Pallarès
Jul 3, 2013·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Poupak FallahiAlessandro Antonelli
Jun 5, 2013·Biochemical Pharmacology·Pei H CuiMichael Murray
Sep 4, 2012·Acta Pharmacologica Sinica·Wei-Feng MaoChong-Gang Yuan
Jun 24, 2008·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Yuri E Nikiforov
Apr 6, 2011·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Steven I Sherman
Oct 14, 2008·Nature Chemical Biology·Beth ApselZachary A Knight
Oct 5, 2006·Nature Clinical Practice. Oncology·Matthias Drosten, Brigitte M Pützer
May 25, 2007·Nature Reviews. Cancer·Henk M W Verheul, Herbert M Pinedo
May 13, 2008·Nature Reviews. Cancer·Klaus Strebhardt, Axel Ullrich
Oct 4, 2006·Nature Reviews. Drug Discovery·Scott WilhelmSusan Kelley
Jan 12, 2007·The New England Journal of Medicine·Bernard EscudierUNKNOWN TARGET Study Group
May 28, 2009·Thyroid : Official Journal of the American Thyroid Association·UNKNOWN American Thyroid Association Guidelines Task ForceSamuel A Wells
Aug 12, 2008·Thyroid : Official Journal of the American Thyroid Association·Giuliana SalvatoreMassimo Santoro
Sep 24, 2009·Thyroid : Official Journal of the American Thyroid Association·Carmelo NuceraSareh Parangi
Dec 29, 2010·Thyroid : Official Journal of the American Thyroid Association·Libo ChenRuisen Zhu
Jun 29, 2010·Thyroid : Official Journal of the American Thyroid Association·Tirtha Das, Ross Cagan
Jul 5, 2013·Thyroid : Official Journal of the American Thyroid Association·Sophie BroutinJean-Michel Bidart
Nov 30, 2006·Current Opinion in Oncology·Douglas W Ball
Mar 8, 2013·Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]·Kathryn BreakerThomas W Flaig
Apr 16, 2008·Journal of Gastroenterology and Hepatology·Kwang-Hyub Han, Jun Yong Park
Jan 18, 2011·International Journal of Clinical Practice·R LordP J Ross
Jul 16, 2010·Journal of Oncology·Alessandro AntonelliPoupak Fallahi
Jan 1, 2010·Therapeutic Advances in Medical Oncology·Jennifer A Sipos, Manisha H Shah
Nov 14, 2012·Therapeutic Advances in Endocrinology and Metabolism·David A Liebner, Manisha H Shah
Mar 4, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Antonius A MillerMark J Ratain
May 28, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Andrew X ZhuRakesh K Jain
Apr 7, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Elaine T LamManisha H Shah
Jan 6, 2011·PloS One·Patrick A OttAnna C Pavlick

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