Discovery of CGS 27023A, a non-peptidic, potent, and orally active stromelysin inhibitor that blocks cartilage degradation in rabbits.

Article Details

Citation

MacPherson LJ, Bayburt EK, Capparelli MP, Carroll BJ, Goldstein R, Justice MR, Zhu L, Hu S, Melton RA, Fryer L, Goldberg RL, Doughty JR, Spirito S, Blancuzzi V, Wilson D, O'Byrne EM, Ganu V, Parker DT

Discovery of CGS 27023A, a non-peptidic, potent, and orally active stromelysin inhibitor that blocks cartilage degradation in rabbits.

J Med Chem. 1997 Aug 1;40(16):2525-32.

PubMed ID
9258358 [ View in PubMed
]
Abstract

Structure-activity relationships of a lead hydroxamic acid inhibitor of recombinant human stromelysin were systematically defined by taking advantage of a concise synthesis that allowed diverse functionality to be explored at each position in a template. An ex vivo rat model and an in vivo rabbit model of stromelysin-induced cartilage degradation were used to further optimize these analogs for oral activity and duration of action. The culmination of these modifications resulted in CGS 27023A, a potent, orally active stromelysin inhibitor that blocks the erosion of cartilage matrix.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
CGS-27023Interstitial collagenaseKi (nM)337.537Details
N-ISOBUTYL-N-[4-METHOXYPHENYLSULFONYL]GLYCYL HYDROXAMIC ACIDStromelysin-1Ki (nM)1337.537Details