8 research outputs found
Quantitative Characterization of Major Hepatic UDP-Glucuronosyltransferase Enzymes in Human Liver Microsomes: Comparison of Two Proteomic Methods and Correlation with Catalytic Activity
Full text linkData generated by quantitative LC-MS proteomics are only the start and not the endpoint: Optimization of QconCAT-based measurement of hepatic UDP-glucuronosyltransferase enzymes with reference to catalytic activity
No full textQuantitative Characterization of Major Hepatic UDP-Glucuronosyltransferase Enzymes in Human Liver Microsomes:Comparison of Two Proteomic Methods and Correlation with Catalytic Activity
No full textQuantitative Characterization of Major Hepatic UDP-Glucuronosyltransferase Enzymes in Human Liver Microsomes:Comparison of Two Proteomic Methods and Correlation with Catalytic Activity
Get PDFCross-laboratory evaluation of UDP-glucuronosyltransferase (UGT) abundances and correlation with catalytic activity
No full textData Generated by Quantitative Liquid Chromatography-Mass Spectrometry Proteomics Are Only the Start and Not the Endpoint: Optimization of Quantitative Concatemer-Based Measurement of Hepatic Uridine-5â˛-DiphosphateâGlucuronosyltransferase Enzymes with Reference to Catalytic Activity
No full textA Second-Generation Oral SARS-CoVâ2 Main Protease Inhibitor Clinical Candidate for the Treatment of COVID-19
No full textDespite the record-breaking
discovery, development and approval
of vaccines and antiviral therapeutics such as Paxlovid, coronavirus
disease 2019 (COVID-19) remained the fourth leading cause of death
in the world and third highest in the United States in 2022. Here,
we report the discovery and characterization of PF-07817883, a second-generation,
orally bioavailable, SARS-CoV-2 main protease inhibitor with improved
metabolic stability versus nirmatrelvir, the antiviral component of
the ritonavir-boosted therapy Paxlovid. We demonstrate the in vitro pan-human coronavirus antiviral activity and off-target
selectivity profile of PF-07817883. PF-07817883 also demonstrated
oral efficacy in a mouse-adapted SARS-CoV-2 model at plasma concentrations
equivalent to nirmatrelvir. The preclinical in vivo pharmacokinetics and metabolism studies in human matrices are suggestive
of improved oral pharmacokinetics for PF-07817883 in humans, relative
to nirmatrelvir. In vitro inhibition/induction studies
against major human drug metabolizing enzymes/transporters suggest
a low potential for perpetrator drugâdrug interactions upon
single-agent use of PF-07817883
A Second-Generation Oral SARS-CoVâ2 Main Protease Inhibitor Clinical Candidate for the Treatment of COVID-19
No full textDespite the record-breaking
discovery, development and approval
of vaccines and antiviral therapeutics such as Paxlovid, coronavirus
disease 2019 (COVID-19) remained the fourth leading cause of death
in the world and third highest in the United States in 2022. Here,
we report the discovery and characterization of PF-07817883, a second-generation,
orally bioavailable, SARS-CoV-2 main protease inhibitor with improved
metabolic stability versus nirmatrelvir, the antiviral component of
the ritonavir-boosted therapy Paxlovid. We demonstrate the in vitro pan-human coronavirus antiviral activity and off-target
selectivity profile of PF-07817883. PF-07817883 also demonstrated
oral efficacy in a mouse-adapted SARS-CoV-2 model at plasma concentrations
equivalent to nirmatrelvir. The preclinical in vivo pharmacokinetics and metabolism studies in human matrices are suggestive
of improved oral pharmacokinetics for PF-07817883 in humans, relative
to nirmatrelvir. In vitro inhibition/induction studies
against major human drug metabolizing enzymes/transporters suggest
a low potential for perpetrator drugâdrug interactions upon
single-agent use of PF-07817883
