生物活性

• 靶点

  MMP1 Ki:0.4nM

  MMP12 Ki:3.6nM

  MMP14 Ki:13.4nM

  MMP2 Ki:0.5nM

  MMP26 Ki:0.36nM

  更多

• 描述GM 6001 is a broad spectrum MMP inhibitor with Ki values of 0.1nM, 0.2nM, 0.36nM, 0.4nM, 0.5nM, 3.6nM and 3.7nM for MMP-8, MMP-9, MMP-26, MMP-1, MMP-2, MMP-12 and MMP-7^[1]. The tyrosine phosphorylation of EGFR induced by leptin could be significantly attenuated by treatment with 25μM GM6001 for 30min in rat aortic smooth muscle cells, due to the inhibition of proteolytic cleavage of transmembrane precursors via matrix metalloproteinase by GM6001^[2]. Inhibition of MMP-2/MMP-9-mediated NCAM (Neural cell adhesion molecule) proteolysis by administration of 5μg GM6001 through intracerebroventricular route 30 minutes before and 2 h after ischemia attenuated the infarction, behavioral abnormalities of MCAO (middle cerebral artery occlusion) model mice, with suppression on the level of NCAM cleavage product by GM6001 observed^[3].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  HEk293 cells	-	Function assay	-	Inhibition of human recombinant ADAMTS4 expressed in HEk293 cells using FAM-AEwLQGRPISIAK-TAMRA as substrate measured for 15 mins by fluorometric analysis, IC50=0.48 μM	23376997
  human U251 cells	20 μM	Function assay	-	Protection against anthrax PA63-lethal toxin complex-induced cytotoxicity in human U251 cells at 20 uM at 400 ng/ml by MTT test	17537721

• 动物研究
  剂量	Hamster: 20 mg/kg[4] (i.p.) Rat: 1.2 mg/kg[5] (i.p.); 50 mg/kg, 100 mg/kg[6] (i.p.)
  给药途径	i.p.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT03297827	-	-	Recruiting	August 27, 2019	United States, New Mexico ... more >> Department of Neurology, University of New Mexico Recruiting Albuquerque, New Mexico, United States, 87131-0007 Contact: Asad Ikram, MD    505-272-9382    aikram@salud.unm.edu Principal Investigator: Atif Zafar, MD Sub-Investigator: Asad Ikram, MD Collapse <<

• 参考文献

• [1] Grobelny D, Poncz L, et al. Inhibition of human skin fibroblast collagenase, thermolysin, and Pseudomonas aeruginosa elastase by peptide hydroxamic acids. Biochemistry. 1992 Aug 11;31(31):7152-4.

  [2] Chao HH, Hong HJ, et al. Leptin stimulates endothelin-1 expression via extracellular signal-regulated kinase by epidermal growth factor receptor transactivation in rat aortic smooth muscle cells. Eur J Pharmacol. 2007 Nov 14;573(1-3):49-54. Epub 2007 Jul 4.

  [3] Shichi K, Fujita-Hamabe W, et al. Involvement of matrix metalloproteinase-mediated proteolysis of neural cell adhesion molecule in the development of cerebral ischemic neuronal damage. J Pharmacol Exp Ther. 2011 Aug;338(2):701-10.