A Highly Selective Hydantoin Inhibitor of Aggrecanase-1 and Aggrecanase-2 with a Low Projected Human Dose.
Basic Information
ID: ALA4011634
Journal: J Med Chem
Title: A Highly Selective Hydantoin Inhibitor of Aggrecanase-1 and Aggrecanase-2 with a Low Projected Human Dose.
Authors: Durham TB, Marimuthu J, Toth JL, Liu C, Adams L, Mudra DR, Swearingen C, Lin C, Chambers MG, Thirunavukkarasu K, Wiley MR.
Abstract: Aggrecanase-1 and -2 (ADAMTS-4 and ADAMTS-5) are zinc metalloproteases involved in the degradation of aggrecan in cartilage. Inhibitors could provide a means of altering the progression of osteoarthritis. We report the identification of 7 which had good oral pharmacokinetics in rats and showed efficacy in a rat chemical model of osteoarthritis. The projected human dose required to achieve sustained plasma levels ≥10 times the hADAMTS-5 IC50 is 5 mg q.d.
CiteXplore: 28613895
DOI: 10.1021/acs.jmedchem.7b00650
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