Structural analysis identifies imidazo[1,2-b]pyridazines as PIM kinase inhibitors with in vitro antileukemic activity.
|Abstract||Much attention has recently been focused on PIM kinases as potential targets for the treatment of hematopoietic malignancies and some solid cancers. Using protein stability shift assays, we identified a family of imidazo[1,2-b]pyridazines to specifically interact with and inhibit PIM kinases with low nanomolar potency. The high-resolution crystal structure of a PIM1 inhibitor complex revealed that imidazo[1,2-b]pyridazines surprisingly interact w ... [truncated at 450 characters in length]|
|Author||Pogacic, Vanda; Bullock, Alex N; Fedorov, Oleg; et al|
|Subject||Animals Antineoplastic Agents Cell Line, Tumor Chemistry, Pharmaceutical Drug Design Enzyme Inhibitors Humans Inhibitory Concentration 50 Mice Models, Chemical Models, Molecular Protein Binding Protein-Serine-Threonine Kinases Proto-Oncogene Proteins Proto-Oncogene Proteins c-pim-1 Pyridazines Structure-Activity Relationship pharmacology methods chemistry pharmacology antagonists and inhibitors antagonists and inhibitors chemistry|
Targeting group II PAKs in cancer and metastasis.
|Abstract||The p21 activated kinases (PAKs) play an essential role in cell signaling and control a variety of cellular functions including cell motility, survival, angiogenesis and mitosis. PAKs are important regulators in growth factor signaling, cytoskeletal reorganization and growth factor-mediated cell migration. Overexpression of PAKs has been detected in many cancers and linked to increased migration potential, anchorage independent growth and metasta ... [truncated at 450 characters in length]|
|Author||Eswaran, Jeyanthy; Soundararajan, Meera; Knapp, Stefan;|
|Subject||Animals Antineoplastic Agents Apoptosis Cell Transformation, Neoplastic Chemistry, Pharmaceutical Crystallography, X-Ray Cytoskeleton Drug Design Gene Expression Regulation, Neoplastic Humans Mitosis Neoplasm Metastasis Neoplasms Neurons p21-Activated Kinases pharmacology methods methods metabolism metabolism pathology metabolism metabolism|
Crystal structure of the PIM2 kinase in complex with an organoruthenium inhibitor.
|Abstract||The serine/threonine kinase PIM2 is highly expressed in human leukemia and lymphomas and has been shown to positively regulate survival and proliferation of tumor cells. Its diverse ATP site makes PIM2 a promising target for the development of anticancer agents. To date our knowledge of catalytic domain structures of the PIM kinase family is limited to PIM1 which has been extensively studied and which shares about 50% sequence identity with PIM2.|
|Author||Bullock, Alex N; Russo, Santina; Amos, Ann; et al|
|Subject||Binding Sites Chemistry, Pharmaceutical Crystallography, X-Ray Drug Design Enzyme Inhibitors Humans Molecular Structure Protein Conformation Protein Isoforms Protein Structure, Tertiary Proto-Oncogene Proteins c-pim-1 Ruthenium Staurosporine Structure-Activity Relationship methods methods chemistry chemistry chemistry chemistry|