A CB2 receptor inverse agonist
BML-190(IMMA) is a potent and selective CB2 receptor ligand (Ki values = 435 nM)
The cannabinoid receptor (CB1 and CB2) is a member of G-protein coupled receptor (GPCR) which plays a significant role in physiologic processes such as cognitive and immune functions.
In HEK-293 cells expressing human Cb2 receptor, BML-190 promoted the forskoline-stimulated accumulation of cAMP. BML-190 also reduced the basal level production of inositol phosphate the CB(2) receptor and 16z44-expressing cells. [1]
BML-190 played a role in LPS (lipopolysaccharide)-activated inflammation [2] and in lowering human cytokine secretion and monocytic cell neurotoxicity [3]. It activated fibroblastic colony formation [4] and moderated collagen-induce arthritis [5].
参考文献:
[1] New DC, Wong YH.? BML-190 and AM251 act as inverse agonists at the human cannabinoid CB2 receptor: signalling via cAMP and inositol phosphates.? FEBS Lett. 2003 Feb 11;536(1-3):157-60.? PubMed PMID: 12586356.
[2] Chang YH, Lee ST, Lin WW.? Effects of cannabinoids on LPS-stimulated inflammatory mediator release from macrophages: involvement of eicosanoids.? J Cell Biochem.? 2001;81(4):715-23. PubMed PMID: 11329626.
[3] Klegeris A, Bissonnette CJ, McGeer PL.? Reduction of human monocytic cell neurotoxicity and cytokine secretion by ligands of the cannabinoid-type CB2 receptor.? Br J Pharmacol. 2003 Jun;139(4):775-86. PubMed PMID: 12813001; PubMed Central PMCID: PMC1573900.?
[4] Scutt A, Williamson EM.? Cannabinoids stimulate fibroblastic colony formation by bone marrow cells indirectly via CB2 receptors.? Calcif Tissue Int. 2007 Jan;80(1):50-9.? Epub 2007 Jan 4. PubMed PMID: 17205329.
[5] Zhang L, Zhang X, Wu P, Li H, Jin S, Zhou X, Li Y, Ye D, Chen B, Wan J.? BML-111, a lipoxin receptor agonist, modulates the immune response and reduces the severity of collagen-induced arthritis.? Inflamm Res. 2008 Apr;57(4):157-62. doi: 10.?1007/s00011-007-7141-z. PubMed PMID: 18648754.
[6] Zhang Q, Ma P, Cole RB, Wang G.? In vitro metabolism of indomethacin morpholinylamide (BML-190), an inverse agonist for the peripheral cannabinoid receptor (CB(2)) in rat liver microsomes.? Eur J Pharm Sci. 2010 Sep 11;41(1):163-72.? doi: 10.1016/j.ejps.2010.06.004. Epub 2010 Jun 11. PubMed PMID: 20542112; PubMed Central PMCID: PMC2907062.?
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