エキセメスタン

外観

白色～うすい黄色, 結晶性粉末～粉末

用途

ステロイド性アロマターゼ不可逆的阻害剤です（IC50 = 20 nmol/l）。 アロマターゼを不安定化させ、エストロゲンレベルを減少させます。経口活性があります。

用途

エキセメスタンは、第3世代アロマターゼ阻害薬のひとつ。乳癌の治療に用いられる。
レトロゾールまたはアナストロゾールに抵抗性の局所進行性または転移性の閉経後乳癌にエキセメスタンとエベロリムスの併用は有用であった。

用途

非可逆的アロマターゼ阻害作 用を示します

効能

抗悪性腫瘍薬, エストロゲン生合成阻害薬

商品名

アロマシン (ファイザー)

説明

Exemestane was launched in US and other countries for the treatment of estrogendependent tumors and postmenopausal breast cancer. It is a novel steroidal compound structurally related to the natural substrate for the biosynthesis of estrogen, androstanedione, and can be synthesized by methylidenation of androsta-1, 4-dien- 17beta-ol-3-one in 6 position then oxidation of the alcohol function. Exemestane is an irreversible inactivator of the aromatase enzyme system, so inducing in vivo a dose-related sustained suppression of serum estrogen and minimal endocrine activity. It is the first steroidal representative of the third-generation of orally active aromatase inhibitors with a highly potent and selective mechanism of action, displaying good tolerability and safety profile. In rats with DMBA-induced mammary tumors, 10 to 100 mglkg of exemestan administered po twice-daily for 4 weeks resulted in 76 to 88% regression. In women failing anti-estrogen therapy with tamoxifen, this agent has demonstrated high activity in locally advanced or metastatic disease. In addition, it may also have potential for breast cancer prevention.

化学的特性

white to light yellow crystal powder

使用

Labeled Exemestane, intended for use as an internal standard for the quantification of Exemestane by GC- or LC-mass spectrometry.

定義

ChEBI: A 17-oxo steroid that is androsta-1,4-diene-3,17-dione in which the hydrogens at position 6 are replaced by a double bond to a methylene group. A selective inhibitor of the aromatase (oestrogen synthase) system, it is used in the treatment of advanced brea t cancer.

一般的な説明

Exemestane, 6-methylenandrosta-1,4-diene-3,17-dione (Aromasin), is the first steroid-basedaromatase inhibitor approved for the treatment of breastcancer in the United States. It is a mechanism-based inactivatorthat irreversibly inhibits the enzyme. Plasma estrogenlevels are reduced by 85% to 95% within 2 to 3 days, and effectslast 4 to 5 days. Exemestane does not inhibit any of themajor cytochromes P450 and has essentially no interactionwith steroid receptors, with only a very weak affinity for theAR. The 17β-hydroxyexemestane reduction product, however,has much higher affinity for the AR than the parent(still several fold less than DHT, 0.28% for parent vs. 30%for metabolite). The clinical significance of the affinity islikely minimal because of the low levels of the metaboliteproduced.

危険性

A reproductive hazard.