Your browser doesn't support javascript.
loading
Efficacy and mechanism of action of volasertib, a potent and selective inhibitor of Polo-like kinases, in preclinical models of acute myeloid leukemia.
Rudolph, Dorothea; Impagnatiello, Maria Antonietta; Blaukopf, Claudia; Sommer, Christoph; Gerlich, Daniel W; Roth, Mareike; Tontsch-Grunt, Ulrike; Wernitznig, Andreas; Savarese, Fabio; Hofmann, Marco H; Albrecht, Christoph; Geiselmann, Lena; Reschke, Markus; Garin-Chesa, Pilar; Zuber, Johannes; Moll, Jürgen; Adolf, Günther R; Kraut, Norbert.
Affiliation
  • Rudolph D; Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (D.R., M.A.I., U.T.-G., A.W., F.S., M.H.H., C.A., L.G., M.R., P.G.-C., J.M., G.R.A., N.K.); Institute of Molecular Biotechnology, Vienna, Austria (C.B., C.S., D.W.G.); and Research Institute of Molecular Pathology, Vienna, Austria (M.R., J.Z
  • Impagnatiello MA; Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (D.R., M.A.I., U.T.-G., A.W., F.S., M.H.H., C.A., L.G., M.R., P.G.-C., J.M., G.R.A., N.K.); Institute of Molecular Biotechnology, Vienna, Austria (C.B., C.S., D.W.G.); and Research Institute of Molecular Pathology, Vienna, Austria (M.R., J.Z
  • Blaukopf C; Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (D.R., M.A.I., U.T.-G., A.W., F.S., M.H.H., C.A., L.G., M.R., P.G.-C., J.M., G.R.A., N.K.); Institute of Molecular Biotechnology, Vienna, Austria (C.B., C.S., D.W.G.); and Research Institute of Molecular Pathology, Vienna, Austria (M.R., J.Z
  • Sommer C; Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (D.R., M.A.I., U.T.-G., A.W., F.S., M.H.H., C.A., L.G., M.R., P.G.-C., J.M., G.R.A., N.K.); Institute of Molecular Biotechnology, Vienna, Austria (C.B., C.S., D.W.G.); and Research Institute of Molecular Pathology, Vienna, Austria (M.R., J.Z
  • Gerlich DW; Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (D.R., M.A.I., U.T.-G., A.W., F.S., M.H.H., C.A., L.G., M.R., P.G.-C., J.M., G.R.A., N.K.); Institute of Molecular Biotechnology, Vienna, Austria (C.B., C.S., D.W.G.); and Research Institute of Molecular Pathology, Vienna, Austria (M.R., J.Z
  • Roth M; Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (D.R., M.A.I., U.T.-G., A.W., F.S., M.H.H., C.A., L.G., M.R., P.G.-C., J.M., G.R.A., N.K.); Institute of Molecular Biotechnology, Vienna, Austria (C.B., C.S., D.W.G.); and Research Institute of Molecular Pathology, Vienna, Austria (M.R., J.Z
  • Tontsch-Grunt U; Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (D.R., M.A.I., U.T.-G., A.W., F.S., M.H.H., C.A., L.G., M.R., P.G.-C., J.M., G.R.A., N.K.); Institute of Molecular Biotechnology, Vienna, Austria (C.B., C.S., D.W.G.); and Research Institute of Molecular Pathology, Vienna, Austria (M.R., J.Z
  • Wernitznig A; Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (D.R., M.A.I., U.T.-G., A.W., F.S., M.H.H., C.A., L.G., M.R., P.G.-C., J.M., G.R.A., N.K.); Institute of Molecular Biotechnology, Vienna, Austria (C.B., C.S., D.W.G.); and Research Institute of Molecular Pathology, Vienna, Austria (M.R., J.Z
  • Savarese F; Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (D.R., M.A.I., U.T.-G., A.W., F.S., M.H.H., C.A., L.G., M.R., P.G.-C., J.M., G.R.A., N.K.); Institute of Molecular Biotechnology, Vienna, Austria (C.B., C.S., D.W.G.); and Research Institute of Molecular Pathology, Vienna, Austria (M.R., J.Z
  • Hofmann MH; Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (D.R., M.A.I., U.T.-G., A.W., F.S., M.H.H., C.A., L.G., M.R., P.G.-C., J.M., G.R.A., N.K.); Institute of Molecular Biotechnology, Vienna, Austria (C.B., C.S., D.W.G.); and Research Institute of Molecular Pathology, Vienna, Austria (M.R., J.Z
  • Albrecht C; Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (D.R., M.A.I., U.T.-G., A.W., F.S., M.H.H., C.A., L.G., M.R., P.G.-C., J.M., G.R.A., N.K.); Institute of Molecular Biotechnology, Vienna, Austria (C.B., C.S., D.W.G.); and Research Institute of Molecular Pathology, Vienna, Austria (M.R., J.Z
  • Geiselmann L; Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (D.R., M.A.I., U.T.-G., A.W., F.S., M.H.H., C.A., L.G., M.R., P.G.-C., J.M., G.R.A., N.K.); Institute of Molecular Biotechnology, Vienna, Austria (C.B., C.S., D.W.G.); and Research Institute of Molecular Pathology, Vienna, Austria (M.R., J.Z
  • Reschke M; Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (D.R., M.A.I., U.T.-G., A.W., F.S., M.H.H., C.A., L.G., M.R., P.G.-C., J.M., G.R.A., N.K.); Institute of Molecular Biotechnology, Vienna, Austria (C.B., C.S., D.W.G.); and Research Institute of Molecular Pathology, Vienna, Austria (M.R., J.Z
  • Garin-Chesa P; Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (D.R., M.A.I., U.T.-G., A.W., F.S., M.H.H., C.A., L.G., M.R., P.G.-C., J.M., G.R.A., N.K.); Institute of Molecular Biotechnology, Vienna, Austria (C.B., C.S., D.W.G.); and Research Institute of Molecular Pathology, Vienna, Austria (M.R., J.Z
  • Zuber J; Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (D.R., M.A.I., U.T.-G., A.W., F.S., M.H.H., C.A., L.G., M.R., P.G.-C., J.M., G.R.A., N.K.); Institute of Molecular Biotechnology, Vienna, Austria (C.B., C.S., D.W.G.); and Research Institute of Molecular Pathology, Vienna, Austria (M.R., J.Z
  • Moll J; Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (D.R., M.A.I., U.T.-G., A.W., F.S., M.H.H., C.A., L.G., M.R., P.G.-C., J.M., G.R.A., N.K.); Institute of Molecular Biotechnology, Vienna, Austria (C.B., C.S., D.W.G.); and Research Institute of Molecular Pathology, Vienna, Austria (M.R., J.Z
  • Adolf GR; Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (D.R., M.A.I., U.T.-G., A.W., F.S., M.H.H., C.A., L.G., M.R., P.G.-C., J.M., G.R.A., N.K.); Institute of Molecular Biotechnology, Vienna, Austria (C.B., C.S., D.W.G.); and Research Institute of Molecular Pathology, Vienna, Austria (M.R., J.Z
  • Kraut N; Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (D.R., M.A.I., U.T.-G., A.W., F.S., M.H.H., C.A., L.G., M.R., P.G.-C., J.M., G.R.A., N.K.); Institute of Molecular Biotechnology, Vienna, Austria (C.B., C.S., D.W.G.); and Research Institute of Molecular Pathology, Vienna, Austria (M.R., J.Z
J Pharmacol Exp Ther ; 352(3): 579-89, 2015 Mar.
Article in En | MEDLINE | ID: mdl-25576074
ABSTRACT
Polo-like kinase 1 (Plk1), a member of the Polo-like kinase family of serine/threonine kinases, is a key regulator of multiple steps in mitosis. Here we report on the pharmacological profile of volasertib, a potent and selective Plk inhibitor, in multiple preclinical models of acute myeloid leukemia (AML) including established cell lines, bone marrow samples from AML patients in short-term culture, and subcutaneous as well as disseminated in vivo models in immune-deficient mice. Our results indicate that volasertib is highly efficacious as a single agent and in combination with established and emerging AML drugs, including the antimetabolite cytarabine, hypomethylating agents (decitabine, azacitidine), and quizartinib, a signal transduction inhibitor targeting FLT3. Collectively, these preclinical data support the use of volasertib as a new therapeutic approach for the treatment of AML patients, and provide a foundation for combination approaches that may further improve and prolong clinical responses.
Subject(s)
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pteridines / Leukemia, Myeloid, Acute / Proto-Oncogene Proteins / Protein Serine-Threonine Kinases / Cell Cycle Proteins / Protein Kinase Inhibitors Limits: Animals / Female / Humans Language: En Journal: J Pharmacol Exp Ther Year: 2015 Type: Article
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pteridines / Leukemia, Myeloid, Acute / Proto-Oncogene Proteins / Protein Serine-Threonine Kinases / Cell Cycle Proteins / Protein Kinase Inhibitors Limits: Animals / Female / Humans Language: En Journal: J Pharmacol Exp Ther Year: 2015 Type: Article