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.
화학적 성질
white to light yellow crystal powder
용도
Labeled Exemestane, intended for use as an internal standard for the quantification of Exemestane by GC- or LC-mass spectrometry.
정의
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.
일반 설명
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.
