title: Design, synthesis and structure activity relationship of potent pan-PIM kinase inhibitors derived from the pyridyl carboxamide scaffold.
abstract: The Pim proteins (1, 2 and 3) are serine/threonine kinases that have been found to be upregulated in many hematological malignancies and solid tumors. As a result of overlapping functions among the three isoforms, inhibition of all three Pim kinases has become an attractive strategy for cancer therapy. Herein we describe our efforts in identifying potent pan-PIM inhibitors that are derived from our previously reported pyridyl carboxamide scaffold as part of a medicinal chemistry strategy to address metabolic stability.
authors.affiliation: Global Discovery Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, United States. Electronic address: gisele.nishiguchi@novartis.com.
authors.forename: Gisele A
authors.initials: GA
authors.lastname: Nishiguchi
authors.affiliation: Global Discovery Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, United States.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Burger
authors.affiliation: Global Discovery Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, United States.
authors.forename: Wooseok
authors.initials: W
authors.lastname: Han
authors.affiliation: Global Discovery Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, United States.
authors.forename: Jiong
authors.initials: J
authors.lastname: Lan
authors.affiliation: Global Discovery Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, United States.
authors.forename: Gordana
authors.initials: G
authors.lastname: Atallah
authors.affiliation: Global Discovery Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, United States.
authors.forename: Victoriano
authors.initials: V
authors.lastname: Tamez
authors.affiliation: Global Discovery Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, United States.
authors.forename: Mika
authors.initials: M
authors.lastname: Lindvall
authors.affiliation: Global Discovery Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, United States.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Bellamacina
authors.affiliation: Oncology, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, United States.
authors.forename: Pablo
authors.initials: P
authors.lastname: Garcia
authors.affiliation: Oncology, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Feucht
authors.affiliation: Oncology, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, United States.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Zavorotinskaya
authors.affiliation: Oncology, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, United States.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Global Discovery Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, United States.
authors.forename: Kent
authors.initials: K
authors.lastname: Wong
mesh_terms: D000577:Amides / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D015195:Drug Design; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D047428:Protein Kinase Inhibitors; D051573:Proto-Oncogene Proteins c-pim-1; C406031:proto-oncogene proteins pim
keywords: Hematological malignancies; Pim kinase; pan-PIM kinase inhibitor