362-05-0 Usage
Description
2-HYDROXYESTRADIOL, also known as a metabolite of Estradiol, is a 2-hydroxy steroid that consists of 17beta-estradiol with an additional hydroxy group at position 2. It is characterized by its pale yellow solid appearance and plays a significant role in various biological processes.
Uses
Used in Pharmaceutical Industry:
2-HYDROXYESTRADIOL is used as a pharmaceutical compound for its potential therapeutic applications. As a metabolite of Estradiol, it may have implications in hormone regulation and could be utilized in the development of treatments for hormone-related conditions.
Used in Research and Development:
In the field of research and development, 2-HYDROXYESTRADIOL serves as an essential compound for studying the effects of Estradiol and its metabolites on various biological systems. This can lead to a better understanding of hormone function and the development of new drugs targeting hormone-related disorders.
Used in Analytical Chemistry:
2-HYDROXYESTRADIOL can be used as a reference compound in analytical chemistry for the development and validation of methods to detect and quantify steroid hormones and their metabolites. This is crucial for monitoring hormone levels in various clinical and environmental samples.
Used in Endocrinology:
In the field of endocrinology, 2-HYDROXYESTRADIOL is used as a research tool to study the role of Estradiol and its metabolites in hormone regulation, reproductive health, and other endocrine functions. This can contribute to the development of targeted therapies for endocrine disorders.
Used in Toxicology:
2-HYDROXYESTRADIOL may also be used in toxicology studies to investigate the potential toxic effects of Estradiol and its metabolites on various organs and systems. This can help in understanding the risks associated with exposure to these compounds and inform safety guidelines.
Biological Activity
2-hydroxyestradiol is an angiogenesis inhibitor via the hif-1a pathway.hif-1a, a basic helix-loop-helix pas domain containing protein, is reported as the master transcriptional regulator of cellular and developmental response to hypoxia.
in vitro
in vitro evidences suggested that most of the cellular effects of 2-hydroxyestradiol were mediated by 2-methoxyestradiol, a metabolite of 2-hydroxyestradiol as an anti-cancer agent acting as an angiogenesis inhibitor via the hif-1a pathway. inhibition of catechol-o-methyltransferase (comt), the enzyme methylating 2-hydroxyestradiol to 2-methoxyestradiol, blocked the ability of 2-hydroxyestradiol to inhibit growth of vascular smooth muscle cells, cardiac fibroblasts, as well as renal mesangial cells. moreover, 2-hydroxyestradiol could inhibit vascular smooth muscle cell growth in cells obtained from wild-type mice but not in cells cultured from comt knockout mice. in contrast to 2ohe, treatment of vascular smooth muscle cells with 2-methoxyestradiol inhibited serum-induced growth of cells from both wild-type and comtknockout mice [1].
in vivo
animal study showed that after administration of 2-hydroxyestradiol, plasma levels of 2-hydroxyestradiol declined extremely rapidly. concomitant with the disappearance of 2-hydroxyestradiol, 2-methoxyestradiol occurred and then declined. after administration of 2-methoxyestradiol, plasma levels of 2meoe declined with a plasma cl of 50 ml min(-1) kg(-1). we could not detect 2-hydroxyestradiol in plasma from rats receiving 2-methoxyestradiol. thus, the authors conclude that the conversion of 2-hydroxyestradiol to 2-methoxyestradiol was so efficient, and the administration of 2-hydroxyestradiol is bioequivalent to administration of 2-methoxyestradiol itself [1].
references
[1] zacharia, l. c.,piché, c.a.,fielding, r.m., et al. 2-hydroxyestradiol is a prodrug of 2-methoxyestradiol. journal of pharmacology and experimental therapeutics 309(3), 1093-1097 (2004).
Check Digit Verification of cas no
The CAS Registry Mumber 362-05-0 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 3,6 and 2 respectively; the second part has 2 digits, 0 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 362-05:
(5*3)+(4*6)+(3*2)+(2*0)+(1*5)=50
50 % 10 = 0
So 362-05-0 is a valid CAS Registry Number.
InChI:InChI=1/C18H24O3/c1-18-7-6-11-12(14(18)4-5-17(18)21)3-2-10-8-15(19)16(20)9-13(10)11/h8-9,11-12,14,17,19-21H,2-7H2,1H3/t11-,12+,14-,17-,18-/m0/s1
362-05-0Relevant articles and documents
Short synthesis of 2-methoxyestradiol and 2-hydroxyestradiol
Kiuru, Paula S.,Waehaelae, Kristiina
, p. 373 - 375 (2003)
The estrogen metabolite 2-methoxyestradiol was synthesized from estradiol bis-THP-ether which was 2-hydroxylated using the superbase LIDAKOR, trimethyl borate, and H2O2, then methylated and deprotected to obtain 2-methoxyestradiol in three steps and 61% yield. 2-Hydroxyestradiol was obtained by deprotecting the 2-hydroxyestradiol bis-THP-ether from the first step.
Gelbke et al.
, p. 205 (1973)
Nitidine chloride-induced CYP1 enzyme inhibition and alteration of estradiol metabolism
Mao, Xu,Wang, Jian,Wang, Qian,Yang, Lan,Li, Yilin,Lin, Hao,Peng, Ying,Zheng, Jiang
, p. 919 - 927 (2019)
The cytochrome P450 (P450) 1 family is an important phase I enzyme involved in carcinogen activation. Nitidine chloride (NC) is a pharmacologically active alkaloid with polyaromatic hydrocarbon found in the roots of Zanthoxylum nitidum (Roxb.) DC, a traditional medicinal herb widely used in China. We examined the inhibitory effects of NC on CYP1A1, 1B1, and 1A2. NC significantly inhibited CYP1A1- and 1B1-catalyzed ethoxyresorufin O-deethylation activity (IC50 5 0.28±0.06 and 0.32±0.02 mM, respectively) in a concentration- dependent manner, but only showed slight inhibition of CYP1A2 activity (IC50 > 50 mM). Kinetic analysis revealed that NC competitively inhibited CYP1B1 with a Ki value of 0.47±0.05 mM, whereas NC caused a mixed type of inhibition on CYP1A1 with Ki and KI values of 0.14±0.04 and 0.19±0.09 mM, respectively. The observed enzyme inhibition neither required NADPH nor revealed time dependency. Molecular docking manifested the generation of strong hydrogen-bonding interactions of Ser116 in CYP1A1 and Ser127 in CYP1B1 with methoxy moiety of NC. Additionally, NC-induced alteration of estradiol (E2) metabolism was also investigated in the present study. Hydroxyestradiols, including 2-hydroxyestradiol [(2-OHE2) nontoxic] and 4-hydroxyestradiol [(4-OHE2) genotoxic] generated in recombinant enzyme incubation systems and cultured MCF-7 cells were analyzed, and NC was found to preferentially inhibit the nontoxic 2-hydroxylation activity of E2 mediated by CYP1A1. In conclusion, NCwas a mixed type inhibitor of CYP1A1 and a competitive inhibitor of CYP1B1. The remarkable inhibition on E2 2-hydroxylation might increase the risk of 4- OHE2-induced genotoxicity.
A methoxyflavonoid, chrysoeriol, selectively inhibits the formation of a carcinogenic estrogen metabolite in MCF-7 breast cancer cells
Takemura, Hitomi,Uchiyama, Harue,Ohura, Takeshi,Sakakibara, Hiroyuki,Kuruto, Ryoko,Amagai, Takashi,Shimoi, Kayoko
experimental part, p. 70 - 76 (2011/02/22)
A 17β-estradiol (E2) is hydrolyzed to 2-hydroxy-E2 (2-OHE2) and 4-hydroxy-E2 (4-OHE2) via cytochrome P450 (CYP) 1A1 and 1B1, respectively. In estrogen target tissues including the mammary gland, ovaries, and uterus, CYP1B1 is highly expressed, and 4-OHE2 is predominantly formed in cancerous tissues. In this study, we investigated the inhibitory effects of chrysoeriol (luteorin-3′-methoxy ether), which is a natural methoxyflavonoid, against activity of CYP1A1 and 1B1 using in vitro and cultured cell techniques. Chrysoeriol selectively inhibited human recombinant CYP1B1-mediated 7-ethoxyresorufin-O-deethylation (EROD) activity 5-fold more than that of CYP1A1-mediated activity in a competitive manner. Additionally, chrysoeriol inhibited E2 hydroxylation was catalyzed by CYP1B1, but not by CYP1A1. Methylation of 4-OHE2, which is thought to be a detoxification process, was not affected by the presence of chrysoeriol. In human breast cancer MCF-7 cells, chrysoeriol did not affect the gene expression of CYP1A1 and 1B1, but significantly inhibited the formation of 4-methoxy E2 without any effects on the formation of 2-methoxy E2. In conclusion, we present the first report to show that chrysoeriol is a chemopreventive natural ingredient that can selectively inhibit CYP1B1 activity and prevent the formation of carcinogenic 4-OHE2 from E2..
