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