A first-in-class cannabinoid analog called lenabasum that is a CB2 agonist is being developed as an inflammation-resolving drug candidate. Thus far, specific therapeutic targets include scleroderma, cystic fibrosis, dermatomyositis, and lupus, all of which represent unmet medical needs. Two somewhat-independent molecular mechanisms for this type of action are here proposed. Both pathways initially involve the release of free arachidonic acid after activation of the CB2 receptor and phospholipase A2 by lenabasum. The pathways then diverge into a cyclooxygenase 2–mediated and a lipoxygenase-mediated route. The former leads to increased levels of the cyclopentenone prostaglandin 15-deoxy-Δ^12,14-prostaglandin-J₂ that can activate the NLPR3 inflammasome, which in turn releases caspase-3, leading to apoptosis and the resolution of chronic inflammation. The lipoxygenase-mediated pathway stimulates the production of lipoxin A₄ as well as other signaling molecules called specialized proresolving mediators. These also have inflammation-resolving actions. It is not well understood under which conditions each of these mechanisms operates and whether there is crosstalk between them. Thus, much remains to be learned about the mechanisms describing the actions of lenabasum.

中文翻译：

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Lenabasum消炎作用的分子机制

作为CB2激动剂的一流大麻素类似物lenabasum正在开发中，它可以作为消炎药的候选药物。迄今为止，特定的治疗靶标包括硬皮病，囊性纤维化，皮肌炎和狼疮，所有这些都代表未满足的医疗需求。在此提出了两种与这种作用无关的分子机理。这两种途径最初都涉及通过lenabasum激活CB2受体和磷脂酶A2后释放游离花生四烯酸。然后，这些途径分为环氧合酶2介导的和脂氧合酶介导的途径。前者导致增加的环戊烯酮前列腺素的水平15-脱氧Δ ^12,14 -前列腺素-J ₂可以激活NLPR3炎性体，进而释放caspase-3，从而导致细胞凋亡和慢性炎症的消退。脂氧合酶介导的途径刺激脂蛋白A ₄以及其他信号分子的生成，这些分子称为专门的前分解介体。这些也具有消炎作用。这些机制中的每一种在什么条件下运行以及它们之间是否存在串扰，人们还不太了解。因此，关于描述灵芝活性的机制仍有许多知识要学习。