Minimising the potential for metabolic activation in drug discovery
AS Kalgutkar, JR Soglia - Expert opinion on drug metabolism & …, 2005 - Taylor & Francis
Investigations into the role of bioactivation in the pathogenesis of xenobiotic-induced toxicity
have been a major area of research since the link between reactive metabolites and …
have been a major area of research since the link between reactive metabolites and …
High throughput ADME screening: practical considerations, impact on the portfolio and enabler of in silico ADME models
…, M Snyder, SJ Steyn, JR Soglia… - Current drug …, 2008 - ingentaconnect.com
Evaluation and optimization of drug metabolism and pharmacokinetic data plays an important
role in drug discovery and development and several reliable in vitro ADME models are …
role in drug discovery and development and several reliable in vitro ADME models are …
Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells
…, J Proctor, N Kosmider, K White, H Stern, J Soglia… - Nature, 2016 - nature.com
Recent clinical trials using immunotherapy have demonstrated its potential to control cancer
by disinhibiting the immune system. Immune checkpoint blocking (ICB) antibodies against …
by disinhibiting the immune system. Immune checkpoint blocking (ICB) antibodies against …
Discovery of N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide, an Agonist of the α7 Nicotinic Acetylcholine Receptor, for the Potential Treatment …
…, KK Cook, SB Sands, SX Zhao, JR Soglia… - Journal of medicinal …, 2006 - ACS Publications
N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide (14, PHA-543,613), a
novel agonist of the α7 neuronal nicotinic acetylcholine receptor (α7 nAChR), has been …
novel agonist of the α7 neuronal nicotinic acetylcholine receptor (α7 nAChR), has been …
Can in vitro metabolism-dependent covalent binding data in liver microsomes distinguish hepatotoxic from nonhepatotoxic drugs? An analysis of 18 drugs with …
RS Obach, AS Kalgutkar, JR Soglia… - Chemical research in …, 2008 - ACS Publications
In vitro covalent binding assessments of drugs have been useful in providing retrospective
insights into the association between drug metabolism and a resulting toxicological response. …
insights into the association between drug metabolism and a resulting toxicological response. …
Discovery of a selective phosphoinositide-3-kinase (PI3K)-γ inhibitor (IPI-549) as an immuno-oncology clinical candidate
…, CM Martin, JG Hoyt, JR Soglia… - ACS medicinal …, 2016 - ACS Publications
Optimization of isoquinolinone PI3K inhibitors led to the discovery of a potent inhibitor of
PI3K-γ (26 or IPI-549) with >100-fold selectivity over other lipid and protein kinases. IPI-549 …
PI3K-γ (26 or IPI-549) with >100-fold selectivity over other lipid and protein kinases. IPI-549 …
Bioactivation of the nontricyclic antidepressant nefazodone to a reactive quinone-imine species in human liver microsomes and recombinant cytochrome P450 3A4
…, ADN Vaz, ME Lame, KR Henne, J Soglia… - Drug metabolism and …, 2005 - ASPET
The therapeutic benefits of the antidepressant nefazodone have been hampered by several
cases of acute hepatotoxicity/liver failure. Although the mechanism of hepatotoxicity remains …
cases of acute hepatotoxicity/liver failure. Although the mechanism of hepatotoxicity remains …
NVL-520 is a selective, TRK-sparing, and brain-penetrant inhibitor of ROS1 fusions and secondary resistance mutations
ROS1 tyrosine kinase inhibitors (TKI) have been approved (crizotinib and entrectinib) or
explored (lorlatinib, taletrectinib, and repotrectinib) for the treatment of ROS1 fusion–positive …
explored (lorlatinib, taletrectinib, and repotrectinib) for the treatment of ROS1 fusion–positive …
The development of a higher throughput reactive intermediate screening assay incorporating micro-bore liquid chromatography–micro-electrospray ionization …
JR Soglia, SP Harriman, S Zhao, J Barberia… - … of pharmaceutical and …, 2004 - Elsevier
An in vitro reactive intermediate screening assay, incorporating the use of the close analog
of glutathione, glutathione ethyl ester (GSH-EE) as a conjugating agent, was developed to …
of glutathione, glutathione ethyl ester (GSH-EE) as a conjugating agent, was developed to …
Application of a linear ion trap/orbitrap mass spectrometer in metabolite characterization studies: examination of the human liver microsomal metabolism of the non …
…, N Duczak, AS Kalgutkar, ME Lame, JR Soglia - Journal of the American …, 2006 - Springer
We report herein, facile metabolite identification workflow on the anti-depressant
nefazodone, which is derived from accurate mass measurements based on a single run/experimental …
nefazodone, which is derived from accurate mass measurements based on a single run/experimental …