A selective small molecule inhibitor of c-Met kinase inhibits c-Met-dependent phenotypes in vitro and exhibits cytoreductive antitumor activity in vivo.

James G. Christensen, Randall Schreck, Jon Burrows, +13

PubMed

Cancer BiologyTumor BiologyC-met KinaseSignaling PathwayReceptor Tyrosine Kinase +18

Discovery and Preclinical Pharmacology of a Selective ATP-Competitive Akt Inhibitor (GDC-0068) for the Treatment of Human Tumors

James F. Blake, Rui Xu, Josef R. Bencsik, +25

Journal of Medicinal Chemistry

Human TumorsTumor BiologyMedicinal ChemistryProtein Kinase B/aktDownstream Biomarkers +13

Discovery of 2-{3-[2-(1-Isopropyl-3-methyl-1<i>H</i>-1,2–4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-<i>d</i>][1,4]oxazepin-9-yl]-1<i>H</i>-pyrazol-1-yl}-2-methylpropanamide (GDC-0032): A β-Sparing Phosphoinositide 3-Kinase Inhibitor with High Unbound Exposure and Robust in Vivo Antitumor Activity

Chudi Ndubaku, Timothy P. Heffron, Steven T. Staben, +26

Journal of Medicinal Chemistry

Drug TargetUnbound Drug ExposurePharmacotherapyIntrinsic ClearanceTumor Biology +19

The Rational Design of Selective Benzoxazepin Inhibitors of the α-Isoform of Phosphoinositide 3-Kinase Culminating in the Identification of ( <i>S</i> )-2-((2-(1-Isopropyl-1 <i>H</i> -1,2,4-triazol-5-yl)-5,6-dihydrobenzo[ <i>f</i> ]imidazo[1,2- <i>d</i> ][1,4]oxazepin-9-yl)oxy)propanamide (GDC-0326)

Timothy P. Heffron, Robert A. Heald, Chudi Ndubaku, +27

Journal of Medicinal Chemistry

Rational Design of Phosphoinositide 3-Kinase α Inhibitors That Exhibit Selectivity over the Phosphoinositide 3-Kinase β Isoform

Timothy P. Heffron, BinQing Wei, Alan G. Olivero, +18

Journal of Medicinal Chemistry

Peptide ScienceChemical BiologyExhibit SelectivityMolecular PharmacologyMedicinal Chemistry +17

The kinase IRAK4 promotes endosomal TLR and immune complex signaling in B cells and plasmacytoid dendritic cells

Cesar A. Corzo, Eugene Varfolomeev, Audi Setiadi, +42

Science Signaling

Discovery of a Potent (4<i>R</i>,5<i>S</i>)-4-Fluoro-5-methylproline Sulfonamide Transient Receptor Potential Ankyrin 1 Antagonist and Its Methylene Phosphate Prodrug Guided by Molecular Modeling

Huifen Chen, Matthew Volgraf, Steven Do, +27

Journal of Medicinal Chemistry

Drug TargetMolecular PainPharmacotherapyPharmacodynamic ModelingMolecular Pharmacology +16

Structure-based design of thienobenzoxepin inhibitors of PI3-kinase

Steven T. Staben, Michael Siu, Richard Goldsmith, +22

Bioorganic & Medicinal Chemistry Letters

Medicinal ChemistryMedicinePharmacologyRational Drug DesignThienobenzoxepin Inhibitors +3

Optimization of Pan-Pim Kinase Activity and Oral Bioavailability Leading to Diaminopyrazole (GDC-0339) for the Treatment of Multiple Myeloma

Xiaojing Wang, Wesley Blackaby, Vivienne Allen, +31

Journal of Medicinal Chemistry

Pim KinasesPharmacotherapyMetronomic ChemotherapyTumor BiologyPim Kinase Inhibition +16

Discovery of 5-Azaindazole (GNE-955) as a Potent Pan-Pim Inhibitor with Optimized Bioavailability

Xiaojing Wang, Aleksandr Kolesnikov, Suzanne Tay, +17

Journal of Medicinal Chemistry

Pharmaceutical ScienceBioorganic ChemistryPim KinasesPharmacotherapyLead Series +16