An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19
- D. Owen, C. Allerton, Y. Zhu
- Biology, MedicineScience
- 31 July 2021
The discovery and characterization of a drug against the main protease involved in the cleavage of polyproteins involved in viral replication is reported, which can be administered orally, has good selectivity and safety profiles, and protects against infection in a mouse model.
A comprehensive listing of bioactivation pathways of organic functional groups.
- A. Kalgutkar, I. Gardner, S. Harriman
- BiologyCurrent drug metabolism
- 31 May 2005
This review aims to serve as a resource describing the structural diversity of functional groups or structural motifs commonly utilized in drug design efforts as well as experimental approaches that could be taken to evaluate whether a "structural alert" in a new drug candidate undergoes bioactivation to reactive metabolites.
A Novel Mechanism of Cyclooxygenase-2 Inhibition Involving Interactions with Ser-530 and Tyr-385*
- S. Rowlinson, J. Kiefer, L. Marnett
- Chemistry, BiologyJournal of Biological Chemistry
- 14 November 2003
diclofenac inhibition was unaffected by the mutation of Arg-120 to alanine but was dramatically attenuated by the S530A mutation, and mutagenesis experiments suggest Ser-530 is also important in time-dependent inhibition by nimesulide and piroxicam.
Discovery of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide, an agonist of the alpha7 nicotinic acetylcholine receptor, for the potential treatment of cognitive deficits in…
- D. Wishka, Daniel P. Walker, Bruce N. Rogers
- Biology, ChemistryJournal of Medicinal Chemistry
- 10 June 2006
Compound 14 is a potent and selective alpha7 nAChR agonist with an excellent in vitro profile and demonstrates in vivo efficacy in auditory sensory gating and, in an in vivo model to assess cognitive performance, novel object recognition.
Arachidonic Acid Oxygenation by COX-1 and COX-2
- L. Marnett, S. Rowlinson, D. Goodwin, A. Kalgutkar, C. Lanzo
- BiologyJournal of Biological Chemistry
- 13 August 1999
The hypothesis that some of the beneficial effects of NSAIDs may be separable from their side effects by development of isoform-selective inhibitors is dramatically validated by the demonstration that selective COX-2 inhibitors are anti-inflammatory and analgesic but lack the gastric toxicity associated with all currently available NSAIDs.
Mechanism-based inactivation of cytochrome P450 enzymes: chemical mechanisms, structure-activity relationships and relationship to clinical drug-drug interactions and idiosyncratic adverse drug…
- A. Kalgutkar, R. Obach, T. Maurer
- BiologyCurrent drug metabolism
- 31 May 2007
A comprehensive analysis of the biochemical basis and known structure-activity relationships for P 450 inactivation by xenobiotics is described and the current state-of-the-art of the methodology used in predicting the magnitude of DDIs using in vitro P450 inactivation data and human pharmacokinetic parameters is discussed in detail.
Biotransformation reactions of five-membered aromatic heterocyclic rings.
- D. Dalvie, A. Kalgutkar, S. Khojasteh-Bakht, R. Obach, J. O'Donnell
- ChemistryChemical Research in Toxicology
- 7 February 2002
Inhibition of hepatobiliary transport as a predictive method for clinical hepatotoxicity of nefazodone.
- Seva E Kostrubsky, S. Strom, A. Mutlib
- Biology, MedicineToxicological Sciences
- 1 April 2006
It is suggested that inhibition of bile acid transport by nefazodone is an indicator of potential hepatotoxicity in the selection of nonhepatotoxic drug candidates.
Structural alert/reactive metabolite concept as applied in medicinal chemistry to mitigate the risk of idiosyncratic drug toxicity: a perspective based on the critical examination of trends in the…
- A. Stepan, Daniel P. Walker, M. Aleo
- BiologyChemical Research in Toxicology
- 11 July 2011
While RM elimination may be a useful and pragmatic starting point in mitigating idiosyncratic toxicity risks, the analysis suggests a need for a more integrated screening paradigm for chemical hazard identification in drug discovery.
Interactions of nitrogen-containing xenobiotics with monoamine oxidase (MAO) isozymes A and B: SAR studies on MAO substrates and inhibitors.
- A. Kalgutkar, D. Dalvie, N. Castagnoli, T. Taylor
- ChemistryChemical Research in Toxicology
- 20 July 2001
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