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Your search keyword '"Julia M. Ford Pulido"' showing total 2 results
Start Over Author "Julia M. Ford Pulido" Topic aurora kinases
2 results on '"Julia M. Ford Pulido"'

1. Discovery of Highly Potent and Selective Pan-Aurora Kinase Inhibitors with Enhanced in Vivo Antitumor Therapeutic Index

Author

Sheena Quiambao, Ruwanthi N. Gunawardane, Dana Gitnick, Mindy I. Davis, Shawn R. Eichelberger, Mike A. Breider, Robert C. Armstrong, Gang Liu, Lan Tran, Michael F. Gardner, Michael J. Hadd, Julia M. Ford Pulido, Julius L. Apuy, Sunny Abraham, Barbara Belli, Joyce James, Helen Hua, Mark W. Holladay, Troy D. Vickers, Shimin Xu, and Daniel K. Treiber

Subjects
Models, Molecular, Transplantation, Heterologous, Aurora inhibitor, Antineoplastic Agents, Protein Serine-Threonine Kinases, Pharmacology, Histones, Rats, Sprague-Dawley, Rats, Nude, Structure-Activity Relationship, Aurora kinase, Therapeutic index, Aurora Kinases, In vivo, Catalytic Domain, Cell Line, Tumor, Drug Discovery, Animals, Humans, Phosphorylation, Aurora Kinase A, Cell Proliferation, Triazines, Cell growth, Kinase, Chemistry, Stereoisomerism, Rats, Molecular Medicine, Acetanilides, Drug Screening Assays, Antitumor, Neoplasm Transplantation, Cytokinesis, Protein Binding
Abstract

Serine/threonine protein kinases Aurora A, B, and C play essential roles in cell mitosis and cytokinesis. Currently a number of Aurora kinase inhibitors with different isoform selectivities are being evaluated in the clinic. Herein we report the discovery and characterization of 21c (AC014) and 21i (AC081), two structurally novel, potent, kinome-selective pan-Aurora inhibitors. In the human colon cancer cell line HCT-116, both compounds potently inhibit histone H3 phosphorylation and cell proliferation while inducing 8N polyploidy. Both compounds administered intravenously on intermittent schedules displayed potent and durable antitumor activity in a nude rat HCT-116 tumor xenograft model and exhibited good in vivo tolerability. Taken together, these data support further development of both 21c and 21i as potential therapeutic agents for the treatment of solid tumors and hematological malignancies.

Published
2012
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2. Novel series of pyrrolotriazine analogs as highly potent pan-Aurora kinase inhibitors

Author

Michael J. Hadd, Helen Hua, Gang Liu, Dana Gitnick, Troy D. Vickers, Lan Tran, Janice A. Sindac, Joyce James, Zdravko V. Milanov, Robert C. Armstrong, Daniel K. Treiber, Mark W. Holladay, Julia M. Ford Pulido, Merryl D. Cramer, Barbara Belli, Shripad Bhagwat, Alan Dao, and Sunny Abraham

Subjects
medicine.drug_class, Stereochemistry, Clinical Biochemistry, Pharmaceutical Science, Carboxamide, Protein Serine-Threonine Kinases, Mitogen-activated protein kinase kinase, Biochemistry, MAP2K7, Structure-Activity Relationship, Aurora kinase, Aurora Kinases, Drug Discovery, medicine, Protein Kinase Inhibitors, Molecular Biology, Serine/threonine-specific protein kinase, Dose-Response Relationship, Drug, Molecular Structure, biology, Triazines, Chemistry, Cyclin-dependent kinase 4, Kinase, Organic Chemistry, Cyclin-dependent kinase 2, Stereoisomerism, biology.protein, Molecular Medicine
Abstract

The synthesis and SAR for a novel series of pyrrolotriazines as pan-Aurora kinase inhibitors are described. Optimization of the cyclopropane carboxamide terminus of lead compound 1 resulted in analogs with high cellular activity and improved rat PK profiles. Notably, compound 17l demonstrated tumor growth inhibition in a mouse xenograft model.

Published
2011
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