Luffariellolide is an agonist for the RA receptors RAR α, β, and γ.
Retinoids show anti-tumour activity on various cancer cells and thus have been used as important therapeutic agents. However, adverse side effects and retinoic acid (RA) resistance limit its further development.
In vitro: Previous study reported the identification of luffariellolide, a natural marine product activating RA receptors (RARs) with a chemical structure distinct from retinoids by high-throughput screening. Luffariellolide was found to be a novel RAR agonist via inducing co-activator binding to RA receptors, further inhibiting cell growth and regulating RAR target genes in various cancer cells [1].
In vivo: In a previous animal study, paw edema was produced in CD-1 mice by the injection snake venom PLA2 into the hind paw. It was found that luffariellolide and aristolochic acid could reduce the edema but only when coinjected with the PLA2. Similarly, the PAF antagonists, CV-6202 and kadsurenone (coinjected) were also able to reduce the PLA2-induced edema, and high doses of the corticosteroids, dexamethasone and hydrocortisone were also effective [2].
Clinical trial: So far, no clinical study has been conducted.
References:
[1] Wang S, Wang Z, Lin S, Zheng W, Wang R, Jin S, Chen J, Jin L, Li Y. Revealing a natural marine product as a novel agonist for retinoic acid receptors with a unique binding mode and inhibitory effects on cancer cells. Biochem J. 2012 Aug 15;446(1):79-87.
[2] Calhoun, W. ,Yu, J.,Sung, A., et al. Pharmacologic modulation of D-49 phospholipase A2-induced paw edema in the mouse. Agents and Actions 27, 418-421 (1989).