Discovery of CGS 27023A, a non-peptidic, potent, and orally active stromelysin inhibitor that blocks cartilage degradation in rabbits.
Article Details
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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
Drug Target Property Measurement pH Temperature (°C) CGS-27023 Interstitial collagenase Ki (nM) 33 7.5 37 Details N-ISOBUTYL-N-[4-METHOXYPHENYLSULFONYL]GLYCYL HYDROXAMIC ACID Stromelysin-1 Ki (nM) 133 7.5 37 Details