79352-78-6Relevant articles and documents
Acetylshikonin is a novel non-selective cytochrome P450 inhibitor
Shon, Jong Cheol,Phuc, Nguyen Minh,Kim, Won Cheol,Heo, Jae Kyung,Wu, Zhexue,Lee, Hyunyoung,Liu, Kwang-Hyeon
, p. 553 - 556 (2017/12/15)
Acetylshikonin is a biologically active compound with anti-cancer and anti-inflammatory activity, which is isolated from the roots of Lithospermum erythrorhizoma. An inhibitory effect of acetylshikonin against CYP2J2 activity was discovered recently. Based on this result, this study was expanded to evaluate the inhibitory effects of acetylshikonin against nine different cytochrome P450 (P450) isoforms in human liver microsomes (HLMs) using substrate cocktails incubation assay. Acetylshikonin showed a strong inhibitory effect against all P450s tested with IC50 values of 1.4–4.0 μ m. Pre-incubation of acetylshikonin with HLMs and NADPH did not alter the inhibition potency, indicating that acetylshikonin is not a mechanism-based inhibitor. SKF-525A, a widely used non-specific P450 inhibitor, had no inhibitory activity against CYP1A2, 2A6, 2E1 and 2J2, while it showed an inhibitory effect against CYP2B6, CYP2C19 and 2D6 with IC50 values of 2.5, 3.6 and 0.5 μ m, respectively. Our findings indicate that acetylshikonin may be a novel general P450 inhibitor, which could replace SKF-525A.
Engineering Macaca fascicularis cytochrome P450 2C20 to reduce animal testing for new drugs
Rua, Francesco,Sadeghi, Sheila J.,Castrignanò, Silvia,Di Nardo, Giovanna,Gilardi, Gianfranco
, p. 277 - 284 (2013/01/15)
In order to develop in vitro methods as an alternative to P450 animal testing in the drug discovery process, two main requisites are necessary: 1) gathering of data on animal homologues of the human P450 enzymes, currently very limited, and 2) bypassing t
Identification of human cytochrome P450s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data
Li, Xue-Qing,Bjoerkman, Anders,Andersson, Tommy B.,Gustafsson, Lars L.,Masimirembwa, Collen
, p. 429 - 442 (2007/10/03)
Objective: Knowledge about the metabolism of anti-parasitic drugs (APDs) will be helpful in ongoing efforts to optimise dosage recommendations in clinical practise. This study was performed to further identify the cytochrome P450 (CYP) enzymes that metabolise major APDs and evaluate the possibility of predicting in vivo drug clearances from in vitro data. Methods: In vitro systems, rat and human liver microsomes (RLM, HLM) and recombinant cytochrome P450 (rCYP), were used to determine the intrinsic clearance (CLint) and identify responsible CYPs and their relative contribution in the metabolism of 15 commonly used APDs. Results and discussion: CLint determined in RLM and HLM showed low (r2=0.50) but significant (Pint values were scaled to predict in vivo hepatic clearance (CLH) using the 'venous equilibrium model'. The number of compounds with in vivo human CL data after intravenous administration was low (n=8), and the range of CL values covered by these compounds was not appropriate for a reasonable quantitative in vitro-in vivo correlation analysis. Using the CLH predicted from the in vitro data, the compounds could be classified into three different categories: high-clearance drugs (> 70% liver blood flow; amodiaquine, praziquantel, albendazole, thiabendazole), low-clearance drugs (int drug categories. The identified CYPs for some of the drugs provide a basis for how these drugs are expected to behave pharmacokinetically and help in predicting drug-drug interactions in vivo.
