Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells

Olivier De Henau, Matthew Rausch, David A. Winkler, +21

Nature

Hematological MalignancyBlockade TherapyImmunologyImmune Checkpoint InhibitorMyeloid Cells +5

Can In Vitro Metabolism-Dependent Covalent Binding Data in Liver Microsomes Distinguish Hepatotoxic from Nonhepatotoxic Drugs? An Analysis of 18 Drugs with Consideration of Intrinsic Clearance and Daily Dose

R. Scott Obach, Amit S. Kalgutkar, John R. Soglia, +1

Chemical Research in Toxicology

Daily DoseVitro CovalentIntrinsic ClearanceVitro Covalent BindingMedicinal Chemistry +18

Discovery of<i>N</i>-[(3<i>R</i>)-1-Azabicyclo[2.2.2]oct-3-yl]furo[2,3-<i>c</i>]pyridine-5-carboxamide, an Agonist of the α7 Nicotinic Acetylcholine Receptor, for the Potential Treatment of Cognitive Deficits in Schizophrenia:  Synthesis and Structure−Activity Relationship

Donn G. Wishka, Daniel P. Walker, Karen M. Yates, +29

Journal of Medicinal Chemistry

NeuropsychologyCompound 14PsychopharmacologyPharmacotherapySocial Sciences +21

BIOACTIVATION OF THE NONTRICYCLIC ANTIDEPRESSANT NEFAZODONE TO A REACTIVE QUINONE-IMINE SPECIES IN HUMAN LIVER MICROSOMES AND RECOMBINANT CYTOCHROME P450 3A4

Amit S. Kalgutkar, Alfin D. N. Vaz, Mary E. Lame, +8

Drug Metabolism and Disposition

Discovery of a Selective Phosphoinositide-3-Kinase (PI3K)-γ Inhibitor (IPI-549) as an Immuno-Oncology Clinical Candidate

Catherine A. Evans, Tao Liu, André Lescarbeau, +22

ACS Medicinal Chemistry Letters

ImmunologyRobust Inhibition-γ InhibitorPharmacotherapyImmuno-oncology Clinical Candidate +15

Application of a linear ion trap/orbitrap mass spectrometer in metabolite characterization studies: Examination of the human liver microsomal metabolism of the non-tricyclic anti-depressant nefazodone using data-dependent accurate mass measurements

Scott Peterman, Nicholas Duczak, Amit S. Kalgutkar, +2

Journal of the American Society for Mass Spectrometry

Metabolomic ProfilingPharmacotherapyMetabolite Characterization StudiesMedicinal ChemistryPharmacological Study +17

The development of a higher throughput reactive intermediate screening assay incorporating micro-bore liquid chromatography–micro-electrospray ionization–tandem mass spectrometry and glutathione ethyl ester as an in vitro conjugating agent

John R. Soglia, Shawn Harriman, Sabrina X. Zhao, +4

Journal of Pharmaceutical and Biomedical Analysis

BiochemistryMedicineNatural SciencesBioanalysisMass Spectrometry +11

A Semiquantitative Method for the Determination of Reactive Metabolite Conjugate Levels in Vitro Utilizing Liquid Chromatography−Tandem Mass Spectrometry and Novel Quaternary Ammonium Glutathione Analogues

John R. Soglia, Leonard G. Contillo, Amit S. Kalgutkar, +4

Chemical Research in Toxicology

NADPH-Dependent Covalent Binding of [³H]Paroxetine to Human Liver Microsomes and S-9 Fractions: Identification of an Electrophilic Quinone Metabolite of Paroxetine

Sabrina X. Zhao, Deepak Dalvie, Joan M. Kelly, +5

Chemical Research in Toxicology

S-9 FractionsPharmacotherapyP450 InactivationQuinone SpeciesChemical Biology +18

Metabolic activation of the nontricyclic antidepressant trazodone to electrophilic quinone-imine and epoxide intermediates in human liver microsomes and recombinant P4503A4

Amit S. Kalgutkar, Kirk R. Henne, Mary E. Lame, +5

Chemico-Biological Interactions

BiochemistryMetabolic ActivationMedicinePsychotropic MedicationExperimental Pharmacology +5