Metabolism and disposition of varenicline, a selective α4β2 acetylcholine receptor partial agonist, in vivo and in vitro

…, SS Krueger, BJ Obach, TN O'Connell… - Drug metabolism and …, 2006 - ASPET
The metabolism and disposition of varenicline (7,8,9,10-tetrahydro-6,10-methano-6H-pyrazino[2,3-h][3]benzazepine),
a partial agonist of the nicotinic acetylcholine receptor for the …

[PDF][PDF] A small-molecule anti-secretagogue of PCSK9 targets the 80S ribosome to inhibit PCSK9 protein translation

…, KA Stevens, BA Maguire, TN O'Connell… - Cell chemical …, 2016 - cell.com
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that downregulates
low-density lipoprotein (LDL) receptor (LDL-R) levels on the surface of hepatocytes, …

Integrating intramolecular hydrogen bonding (IMHB) considerations in drug discovery using ΔlogP as a tool

…, G Caron, YA Abramov, TN O'Connell… - Journal of medicinal …, 2013 - ACS Publications
This study demonstrates that ΔlogP oct-tol (difference between logP octanol and logP toluene
) describes compounds propensity to form intramolecular hydrogen bonds (IMHB) and …

Solution-Based Indirect Affinity Selection Mass Spectrometry A General Tool For High-Throughput Screening Of Pharmaceutical Compound Libraries

TN O'Connell, J Ramsay, SF Rieth, MJ Shapiro… - Analytical …, 2014 - ACS Publications
We show here that an automated solution-based affinity selection mass spectrometry (ASMS)
system can be built exclusively from commercially available parts. The value of this …

Discovery and optimization of a novel spiropyrrolidine inhibitor of β-secretase (BACE1) through fragment-based drug design

…, S Noell, CE Oborski, TN O'Connell… - Journal of medicinal …, 2012 - ACS Publications
The aspartyl protease β-secretase, or BACE, has been demonstrated to be a key factor in
the proteolytic formation of Aβ-peptide, a major component of plaques in the brains of …

PF-07059013: a noncovalent modulator of hemoglobin for treatment of sickle cell disease

…, J Narula, JJ Novak, TN O'Connell… - Journal of Medicinal …, 2020 - ACS Publications
Sickle cell disease (SCD) is a genetic disorder caused by a single point mutation (β6 Glu →
Val) on the β-chain of adult hemoglobin (HbA) that results in sickled hemoglobin (HbS). In …

Identification of a novel glutathione adduct of diclofenac, 4′-hydroxy-2′-glutathion-deschloro-diclofenac, upon incubation with human liver microsomes

JY Li, Y Chen, MP Deninno, TN O'Connell… - Drug metabolism and …, 2005 - ASPET
Clinical use of the nonsteroidal anti-inflammatory drug diclofenac (DF) is associated with an
incidence of idiosyncratic hepatoxicity. The formation of reactive metabolites of DF in vivo …

Aminopyrazole carboxamide bruton's tyrosine kinase inhibitors. irreversible to reversible covalent reactive group tuning

…, JS Miyashiro, S Mohan, TN O'Connell… - ACS Medicinal …, 2018 - ACS Publications
Potent covalent inhibitors of Bruton’s tyrosine kinase (BTK) based on an aminopyrazole
carboxamide scaffold have been identified. Compared to acrylamide-based covalent reactive …

Characterization of novel dihydrothienopyridinium and thienopyridinium metabolites of ticlopidine in vitro: role of peroxidases, cytochromes P450, and monoamine …

DK Dalvie, TN O'Connell - Drug metabolism and disposition, 2004 - ASPET
Ticlopidine is an agent that inhibits adenosine diphosphate-induced platelet aggregation.
Metabolic studies with ticlopidine have indicated that the principal routes of metabolism are N-…

Novel erythromycins from a recombinant Saccharopolyspora erythraea strain NRRL 2338 pIG1 I. Fermentation, isolation and biological activity

…, EL McCormick, RA Monday, TN O'CONNELL… - The Journal of …, 1998 - jstage.jst.go.jp
In a previous report, a plasmid, pIG1, which contained the loading domain from the Streptomyces
avermitilis polyketide synthase (PKS), promoters from Streptomyces coelicolor and the …