Background:

IC50: 89% inhibition at 10μg/mL

CL 82198 is a selective MMP-13 inhibitor.

Matrix metalloproteinases (MMPs) are involved in the degradation of the extracellular matrix associated with normal tissue remodeling processes such as wound healing, pregnancy, and angiogenesis. Expression and activity of MMPs is highly controlled due to their degradative nature where the apparent loss in this regulation leads to the pathological destruction of connective tissue and the ensuing disease state.

In vitro: CL-82198 was identified as a weak inhibitor against MMP-13 and demonstrated no activity against MMP-1, MMP-9, or the related enzyme TACE. Bearing drug-like properties, CL-82198 was regarded as an ideal candidate for optimization of enzyme potency and selectivity. In NMR binding studies, it was shown that CL-82198 bound within the entire S1’ pocket of MMP-13, which was the basis of its selectivity against MMP-1, MMP-9, and TACE [1].

In vivo: To investigate the contribution of MMP-13 down-regulation during gastroprotection by acetaminophen, the effects of CL-82198 on IBP-induced gastric damage were evaluated. Results showed that CL-82198 decreased gastric lesions in a dose-dependent manner in the presence of IBP. Compared with IBP administration alone, CL-82198 administered at 0.2 and 1.0 mg/kg resulted in 40.3% and 72.1% decrease in gastric lesion, respectively [1].

Clinical trial: N/A

参考文献:
[1] James M.  Chen,Frances C. Nelson,Jeremy I. Levin,Dominick Mobilio,Franklin J. Moy,Ramaswamy Nilakantan,Arie Zask,andRobert Powers. Structure-Based Design of a Novel, Potent, and Selective Inhibitor for MMP-13 Utilizing NMR Spectroscopy and Computer-Aided Molecular Design. J. Am. Chem. Soc.,2000,122(40), pp 9648–9654
[2] Fukushima E,Monoi N,Mikoshiba S,Hirayama Y,Serizawa T,Adachi K,Koide M,Ohdera M,Murakoshi M,Kato H.  Protective effects of acetaminophen on ibuprofen-induced gastric mucosal damage in rats with associated suppression of matrix metalloproteinase. J Pharmacol Exp Ther.2014 Apr;349(1):165-73.