AM630

AM630 is a potent and selective CB₂ receptor inverse agonist ^[1]. AM630 enhances forskolin-stimulated cAMP levels, inhibits [¹⁴S]-GTPγS binding, and antagonizes the inhibitory effects of the CB₂ agonist CP55940 on cAMP ^[2-3]. AM630 is commonly used in anxiety and neurobehavioral research ^[4].

In RAW264.7 mouse macrophage cells, AM630 (200nM; 5d) inhibits osteoclast differentiation ^[5]. In hCB₂ CHO cells, AM630 (10μM; 24h) enhances forskolin-stimulated cAMP production ^[6]. In C2C12 myoblasts, pretreatment with AM630 (5μM; 2h) combined with anandamide significantly increased COX activity and COX-1 protein expression ^[7].

In CD-1 mice, AM630 (0.3mg/kg, 1mg/kg, 10mg/kg; ip; 1.5h) increased cortical FADD, Bax, cytochrome c, and PARP cleavage ^[8]. AM630 (1 mg/kg; ip; single injection) treatment reduces the LC3-II/LC3-I ratio and increases SQSTM1/p62 expression in the bladders of mice with cyclophosphamide (CYP)-induced cystitis ^[9].

References:
[1]. Ross R A, Brockie H C, Stevenson L A, et al. Agonist-inverse agonist characterization at CB1 and CB2 cannabinoid receptors of L759633, L759656 and AM630[J]. British journal of pharmacology, 1999, 126(3): 665.
[2]. Murataeva N, Mackie K, Straiker A. The CB2-preferring agonist JWH015 also potently and efficaciously activates CB1 in autaptic hippocampal neurons[J]. Pharmacological research, 2012, 66(5): 437-442.
[3]. Morgan N H, Stanford I M, Woodhall G L. Functional CB2 type cannabinoid receptors at CNS synapses[J]. Neuropharmacology, 2009, 57(4): 356-368.
[4]. Crowe M S, Nass S R, Gabella K M, et al. The endocannabinoid system modulates stress, emotionality, and inflammation[J]. Brain, behavior, and immunity, 2014, 42: 1-5.
[5]. Li W, Sun Y. Nrf2 is required for suppressing osteoclast RANKL-induced differentiation in RAW 264.7 cells via inactivating cannabinoid receptor type 2 with AM630[J]. Regenerative Therapy, 2020, 14: 191-195.
[6]. Bolognini D, Cascio M G, Parolaro D, et al. AM630 behaves as a protean ligand at the human cannabinoid CB2 receptor[J]. British journal of pharmacology, 2012, 165(8): 2561-2574.
[7]. Kim J, Watkins B A. Cannabinoid receptor antagonists and fatty acids alter endocannabinoid system gene expression and COX activity[J]. The Journal of Nutritional Biochemistry, 2014, 25(8): 815-823.
[8]. Salort G, Alvaro-Bartolome M, Garcia-Sevilla J A. Regulation of cannabinoid CB2 receptor constitutive activity in vivo: repeated treatments with inverse agonists reverse the acute activation of JNK and associated apoptotic signaling in mouse brain[J]. Psychopharmacology, 2017, 234(6): 925-941.
[9]. Liu Q, Wu Z, Liu Y, et al. Cannabinoid receptor 2 activation decreases severity of cyclophosphamide‐induced cystitis via regulating autophagy[J]. Neurourology and Urodynamics, 2020, 39(1): 158-169.

AM630是一种强效且选择性的CB₂受体反向激动剂 ^[1]。AM630可增强毛喉素刺激产生的cAMP水平，抑制[¹⁴S]-GTPγS结合，并拮抗CB₂激动剂CP55940对cAMP的抑制作用 ^[2-3]。AM630常用于焦虑和神经行为研究 ^[4]。

在RAW264.7小鼠巨噬细胞中，AM630（200nM；5d）可抑制破骨细胞分化 ^[5]。在hCB2 CHO细胞中，AM630（10μM；24h）可增强毛喉素刺激产生的cAMP ^[6]。在C2C12成肌细胞中，AM630（5μM；2h）与花生四烯乙醇胺联合预处理可显著提高COX活性和COX-1蛋白表达 ^[7]。

在CD-1小鼠中，AM630（0.3mg/kg，1mg/kg，10mg/kg；ip；1.5h）可增加皮质FADD、Bax、细胞色素c和PARP的裂解 ^[8]。AM630（1mg/kg；ip；单次注射）治疗可降低环磷酰胺（CYP）诱发的膀胱炎小鼠膀胱中的LC3-II/LC3-I比例，并增加SQSTM1/p62的表达 ^[9]。