145414-76-2 Usage
Description
6',7'-Dihydroxybergamottin, also known as 6,7-dihydroxy Bergamottin (6,7-DHB), is a minor metabolite of Bergamottin derived from grapefruit juice. It is a potent inhibitor of the cytochrome P450 3A4 enzyme (CYP3A4), which plays a crucial role in the metabolism of various drugs. The compound has garnered significant attention due to its potential applications in the pharmaceutical industry, particularly in drug metabolism and drug-drug interaction studies.
Uses
Used in Pharmaceutical Industry:
6',7'-Dihydroxybergamottin is used as a research compound for studying the inhibition of cytochrome P450 (CYP)-mediated drug metabolism. Its potent inhibitory effect on CYP3A4 makes it a valuable tool in understanding the role of this enzyme in the metabolism of various drugs and its implications in drug-drug interactions.
Used in Drug Metabolism Studies:
6',7'-Dihydroxybergamottin is employed as an inhibitor of testosterone 6β-hydrolase activity, which is mediated by CYP3A4. This application helps researchers investigate the impact of grapefruit juice ingestion on the plasma concentration of drugs metabolized by the CYP3A subfamily of cytochrome P450 enzymes.
Used in Drug Treatment Regimes:
In cases where a drug is metabolized too quickly by CYP3A4, the administration of grapefruit juice or 6,7-DHB could be advantageous. By inhibiting the enzyme, the plasma concentration of the drug can be increased, potentially enhancing its therapeutic effects.
Used in Drug Interaction Research:
6',7'-Dihydroxybergamottin is used as a model compound to study the effects of grapefruit juice on drug metabolism and the potential for drug-drug interactions. This research is essential for understanding the clinical implications of grapefruit juice consumption during drug treatment regimes and for developing strategies to minimize adverse effects.
Biochem/physiol Actions
CYP3A4 inhibitor.
in vitro
6,7-dhb significantly blocked the testosterone 6β-hydrolase in human liver microsomes and human cyp3a4 expressed in escherichia coli membrane in a time- and concentration-dependent manner. furthermore, 6,7-dhb proved to be a potent nadph- and time-dependent inhibitor of cyp3a4 [1]. 6,7-dhb concentration-dependently inhibited nifedipine (nfp) oxidation in hepg2-gs-3a4 cell, a cell line from hepatoblastoma with overexpression of human cyp3a4 [2].
in vivo
male wistar-st rats were intraduodenally administered with 6,7-dhb at a dose of 3.4 mg/ml. after 4 hours, 6,7-dhb had no significant effects on the nfp plasma concentrations, suggesting that 6,7-dhb had no pharmacokinetic effect on the rats [3].
IC 50
25 μm
references
[1]. bellevue, f., woster, p., edwards, d., he, k., & hollenberg, p. synthesis and biological evaluation of 6′,7′-dihydroxybergamottin (6,7-dhb), a naturally occurring inhibitor of cytochrome p450 3a4. bioorganic & medicinal chemistry letters. 1997; 7(20): 2593-2598. [2]. araki, n., tsuruoka, s., hasegawa, g., yanagihara, h., omasa, t., & enosawa, s. et al. inhibition of cyp3a4 by 6′,7′-dihydroxybergamottin in human cyp3a4 over-expressed hepg2 cells. journal of pharmacy and pharmacology. 2012; 64(12): 1715-1721. [3]. mohri, k., & uesawa, y. effects of furanocoumarin derivatives in grapefruit juice on nifedipine pharmacokinetics in rats. pharmaceutical research, 2001;18(2):177-182.
Check Digit Verification of cas no
The CAS Registry Mumber 145414-76-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,4,5,4,1 and 4 respectively; the second part has 2 digits, 7 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 145414-76:
(8*1)+(7*4)+(6*5)+(5*4)+(4*1)+(3*4)+(2*7)+(1*6)=122
122 % 10 = 2
So 145414-76-2 is a valid CAS Registry Number.
145414-76-2Relevant articles and documents
Paradisin C: A new CYP3A4 inhibitor from grapefruit juice
Ohta, Tomihisa,Maruyama, Takuro,Nagahashi, Minoru,Miyamoto, Yasuyo,Hosoi, Shinzo,Kiuchi, Fumiyuki,Yamazoe, Yasushi,Tsukamoto, Sachiko
, p. 6631 - 6635 (2002)
A new furanocoumarin derivative, paradisin C, was isolated from grapefruit juice as an inhibitor of cytochrome P450 (CYP) 3A4. Its stereochemistry was elucidated by spectroscopic methods. The stereochemistries of 17,18-dihydroxybergamottin and 17-epoxybergamottin were also elucidated.
Design, synthesis and evaluation of furanocoumarin monomers as inhibitors of CYP3A4
Row,Brown,Stachulski,Lennard
, p. 1604 - 1610 (2008/02/03)
A number of furanocoumarins isolated from grapefruit juice have been found to inhibit CYP3A4 activity in vitro. In this study, we have designed and synthesised a range of analogues based on bergamottin to investigate the relationship between chemical stru
