Correction to Discovery of Entrectinib: A New 3-Aminoindazole as a Potent Anaplastic Lymphoma Kinase (ALK), c-ros Oncogene 1 Kinase (ROS1), and Pan-Tropomyosin Receptor Kinases (Pan-TRKs) inhibitor

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Entrectinib, a Pan-TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications.

Activated ALK and ROS1 tyrosine kinases, resulting from chromosomal rearrangements, occur in a subset of non-small cell lung cancers (NSCLC) as well as other tumor types and their oncogenic relevance as actionable targets has been demonstrated by the efficacy of selective kinase inhibitors such as crizotinib, ceritinib, and alectinib. More recently, low-frequency rearrangements of TRK kinases h...

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Anaplastic Lymphoma Kinase (ALK)

on chromosome 2p23, and codes for a protein that is expressed in some cells of the central nervous system, but in virtually no other normal human cells. Interest in this protein among diagnostic pathologists has been related to its utility in recognizing a subset of CD30+ anaplastic large cell lymphomas (ALCL's), that show a characteristic t(2;5)(p23;q35) translocation. This translocation resul...

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ALK (anaplastic lymphoma kinase)

Description 1620 amino acids; 177 kDa; after glycosylation, produces a 200 kDa mature glycoprotein; composed of an extracellular domain, a transmembrane domain, a tyrosine kinase domain, and an intracytoplasmic domain in C-term; dimerization. Expression Is tissue specific; mainly in: brain, gut and testis; not in the lymphocytes. Localisation Cell membrane. Function Membrane associated tyrosine...

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Translational pharmacokinetic-pharmacodynamic modeling for an orally available novel inhibitor of anaplastic lymphoma kinase and c-Ros oncogene 1.

An orally available macrocyclic small molecule, PF06463922 [(10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile], is a selective inhibitor of anaplastic lymphoma kinase (ALK) and c-Ros oncogene 1 (ROS1). The objectives of the present study were to characterize the pharmacokinetic-pharmacodynam...

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Correction to Discovery of a Potent and Selective DDR1 Receptor Tyrosine Kinase Inhibitor

Tyrosine Kinase Inhibitor Hyung-Gu Kim, Li Tan, Ellen L. Weisberg, Feiyang Liu, Peter Canning, Hwan-Geun Choi, Scott Ezell, Zheng Zhao, Hong Wu, Jinhua Wang, Anna Mandinova, Alex N. Bullock,* Qingsong Liu,* Sam W. Lee,* and Nathanael S. Gray* ACS Chem. Biol. 2013, 8, 2145−2150. I the reported X-ray cocrystal structure of the DDR1 kinase domain in complex with the inhibitor DDR1-IN-1 (PDB code 4...

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ژورنال

عنوان ژورنال: Journal of Medicinal Chemistry

سال: 2019

ISSN: 0022-2623,1520-4804

DOI: 10.1021/acs.jmedchem.9b01259