Background:

Cannabidiol dimethyl ether (CBDD) is a cannabidiol derivative that potently and selectively inhibits 15-LOX with an IC50 value of 0.28 μM.

15-LOX can oxygenate cholesterol esters in the low-density lipoprotein (LDL) particle. Thus, 15-LOX has been involved in the development of atherosclerosis, and CBDD may be a useful prototype for producing medicines for atherosclerosis [1].

CBDD showed a potent inhibitory effect on the catalytic activity of cytochrome P450 2C19 with an IC50 value of 14.8 μΜ [2]. CBDD inhibited the CYP2B6 activity with the IC50values of 75.7 μM [3]. Cytochrome P450 enzymes have been isolated from numerous mammalian tissues such as liver, kidney, lung, intestine, adrenal cortex. Cytochrome P450 enzymes have also existed in insects, plants, yeasts, and bacteria. Cytochrome P450 has been known to catalyze hydroxylations, epoxidations, N-, S-, and O-dealkylations, N-oxidations, sulfoxidations, dehalogenations, and other reactions [4].

参考文献:
[1] Takeda S, Usami N, Yamamoto I, et al.  Cannabidiol-2′, 6′-dimethyl ether, a cannabidiol derivative, is a highly potent and selective 15-lipoxygenase inhibitor[J]. Drug Metabolism and Disposition, 2009, 37(8): 1733-1737.
[2] Jiang R, Yamaori S, Okamoto Y, et al.  Cannabidiol is a potent inhibitor of the catalytic activity of cytochrome P450 2C19[J]. Drug metabolism and pharmacokinetics, 2013, 28(4): 332-338.
[3] Yamaori S, Maeda C, Yamamoto I, et al.  Differential inhibition of human cytochrome P450 2A6 and 2B6 by major phytocannabinoids[J]. Forensic Toxicology, 2011, 29(2): 117-124.
[4] Groves J T, Han Y Z.  Models and mechanisms of cytochrome P450 action[M]//Cytochrome P450. Springer US, 1995: 3-48.