Matrix metalloproteinases (MMPs) such as MMP13 promote tumour growth and progression by mediating extracellular matrix (ECM) reorganization and regulating the biological activity of cytokines[3]. MMP13 is a vital component for chondrocyte and osteoblast maturation, and is aberrantly expressed in numerous disease states. At the transcriptional level, MMP13 is controlled by many different growth factors and hormones. Most notably, MMP13 is regulated by the vitamin D hormone (1,25(OH)2D3), parathyroid hormone (PTH), and several cytokines[4]. CL-82198 is a selective inhibitor of MMP-13. CL-82198 binds to the entire S1’ pocket of MMP-13, which is the basis for its selectivity towards MMP-13 and the lack of inhibitory activities against other MMPs[5]. CL-82198 (10 μM; 24 hours) significantly reduces LS174 cell migration[6]. CL-82198 decreases CTGF and TGF-β1 protein levels in hepatic stellate cells[7]. CL-82198 is a pharmacologic treatment for preventing osteoarthritis (OA) progression. CL82198 (1-10 mg/kg; i.p.; every other day for 12 weeks) prevents and decelerates MLI-induced osteoarthritis progression[8].
CL-82198 细胞实验
Cell Line
Concentration
Treated Time
Description
References
rat hepatic stellate cells
10 μM
48 h
To examine the effect of MMP-13 inhibition on CTGF and TGF-β1 protein levels, results showed that inhibition of MMP-13 significantly decreased the protein levels of CTGF and its C-terminal fragments as well as active TGF-β1.
J Cell Mol Med. 2017 Dec;21(12):3821-3835
CL-82198 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Medaka (Oryzias latipes)
Osteoporosis model
Immersion
300 μM
Continuous treatment from 7 dpf to 12 dpf
To evaluate the effect of MMP13 inhibitor CL-82198 on bone resorption. Results showed that CL-82198 treatment significantly reduced bone resorption, with fewer lesions in vertebral centra and mostly intact neural arches.
Front Cell Dev Biol. 2022 Feb 21;10:775512
Zebrafish
Streptozotocin-induced diabetic neuropathic pain model
Exposure in water
10 µM
10 consecutive days
To evaluate the reversal effect of CL-82198 on diabetic neuropathic pain, results showed that CL-82198 ameliorated neuralgic behavioral parameters and biochemical changes.
Pharmaceuticals (Basel). 2023 Jan 22;16(2):157
Mice
High-fat/high-sugar diet-induced diabetic neuropathy model
Intraperitoneal injection
5 mg/kg
Every other day for 14 days
To evaluate the therapeutic effect of MMP-13 inhibitor on diabetic neuropathy, results showed that CL-82198 significantly improved tactile sensitivity in mice
J Diabetes Complications. 2018 Mar;32(3):249-257
Zebrafish
Diabetic cerebrovascular damage-associated Alzheimer’s disease model
Not specified
10 μM
21 consecutive days
To evaluate the effect of CL-82198 in a diabetic cerebrovascular damage-associated Alzheimer’s disease model, results showed that CL-82198 improved cognitive dysfunction.
Mar Drugs. 2023 Jul 31;21(8):433
Sprague-Dawley rats
Trauma and hemorrhagic shock model
Intratracheal instillation
100 μM
Pretreatment before trauma
Pretreatment with MMP-13 inhibitor significantly attenuated acute lung injury following trauma/hemorrhagic shock, as reflected by a significant reduction in BAL protein content.
搜索
