Exemestane (trade name Aromasin) is a drug used to treat breast cancer. It is a member of the class of drugs known as aromatase inhibitors. Some breast cancers require estrogen to grow. Those cancers have estrogen receptors (ERs), and are called ER-positive. They may also be called estrogen-responsive, hormonally-responsive, or hormone-receptor-positive. Aromatase is an enzyme that synthesizes estrogen. Aromatase inhibitors block the synthesis of estrogen. This lowers the estrogen level, and slows the growth of cancers.
Pharmacology
Mechanism of action
Exemestane is an oral steroidal aromatase inhibitor that is used in ER-positive breast cancer in addition to surgery and/or radiation in post-menopausal women.
The main source of estrogen is the ovaries in premenopausal women, while in post-menopausal women most of the body's estrogen is produced via the conversion of androgens into estrogen by the aromatase enzyme in the peripheral tissues (i.e. adipose tissue like that of the breast) and a number of sites in the brain. Estrogen is produced locally via the actions of the aromatase enzyme in these peripheral tissues where it acts locally. Any circulating estrogen in post-menopausal women as well as men is the result of estrogen escaping local metabolism and entering the circulatory system.
Exemestane is an irreversible, steroidal aromatase inactivator of type I, structurally related to the natural substrate 4-androstenedione. It acts as a false substrate for the aromatase enzyme, and is processed to an intermediate that binds irreversibly to the active site of the enzyme causing its inactivation, an effect also known as "suicide inhibition." By being structurally similar to enzyme targets, exemestane permanently binds to the enzymes, preventing them from converting androgen into estrogen.
Type II aromatase inhibitors such as anastrozole and letrozole, by contrast, are not steroids and work by interfering with the aromatase's heme.
The estrogen suppression rate for exemestane varies from 35% for estradiol (E2) to 70% for estrone (E1).
Pharmacokinetics
Exemestane is quickly absorbed from the gut, but undergoes a strong first-pass effect in the liver. Highest blood plasma concentrations are reached after 1.2 hours in breast cancer patients and after 2.9 hours in healthy subjects. Maximal aromatase inhibition occurs after two to three days. 90% of the absorbed substance are bound to plasma proteins. The liver enzyme CYP3A4 oxidizes the methylidene group in position 6, and the 17-keto group (on the five-membered ring) is reduced by aldo-keto reductases to an alcohol. Of the resulting metabolites, 40% are excreted via the urine and 40% via the feces within a week. The original substance accounts for only 1% of excretion in the urine. The terminal half-life is 24 hours.
Chemistry
4-Androstenedione for comparison
Like the aromatase inhibitors formestane and atamestane, exemestane is a steroid that is structurally similar to 4-androstenedione, the natural substrate of aromatase. It is distinguished from the natural substance only by the methylidene group in position 6 and an additional double bond in position 1.
Pure exemestane is a white to off-white powder that is soluble in DMSO to at least 20 mg/mL. Optical rotation [α]D is +250 to 300° (per g/100 cm³ and decimetre at 589 nm wavelength).
Detail:
Exemestane
Alias: Aromasin ; Exemestan;Exemestane
Product Category: Pharmaceutical raw materials and intermediates
Assay: 98%min
CAS Registry Number:107868-30-4
Molecular formula: C20H24O2
Molecular Weight:296.40
Appearance: White or Almost White Crystalline Powder
Grade : Pharmaceutical Grade
Storage: Shading, confined preservation
Delivery time :within 24 hours upon receipt of payment
Delivery: EMS, DHL, TNT, FedEx, UPS
Usage: Developed to help fight breast cancer, Aromasin is one of the most powerful estrogen suppressing compounds
Other drugs in same class:Anastrozole,Letrozole,Tamoxifen citrate,Exemestane
COA
TEST ITEMS
|
SPECIFICATION
|
RESULTS
|
Description
|
: White Crystalline Powder
|
White Powder
|
Identification
|
: Positive
|
Positive
|
Assay(by HPLC)
|
: 98.0~102.0%
|
98.64%
|
Absorbance(E1cm)
|
: 465~495
|
482.5
|
Melting Point
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: 191~195°C
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193.5~195.0°C
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Loss On Drying
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: 0.5%max
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0.19%
|
Specific Rotation
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: +288°~ +298°
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+290.2°
|
Residue On Ignition
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: 0.1%max
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0.03%
|
Related Substances
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: Total:1.5%max
|
<1.3%
|
Single:0.5%max
|
<0.4%
| |
Residue Solvents
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: 0.2%max
|
0.10%
|
Heavy Metals
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: 20PPm max
|
<10PPm
|
Conclusion
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The specification conform with enterprise standard.
| |
Package:
0.5kgs/Al-foil bag
1.0kgs/Al-foil bag
2.0kgs/Al-foil bag
5.0 kgs/Al-foil bag
25.0 kgs/drum
or upon customers' request
Application:
1. Exemestane is an oral steroidal aromatase inhibitor that is used in ER-positive breast cancer in addition to surgery and/or radiation in post-menopausal women.
2. Exemestane is an irreversible, steroidal aromatase inactivator, structurally related to the natural substrate androstenedione.
3. It acts as a false substrate for the aromatase enzyme, and is processed to an intermediate that binds irreversibly to the active site of the enzyme causing its inactivation, an effect also known as "suicide inhibition."
4. By being structurally similar to enzyme targets, Exemestane permanently binds to the enzymes, preventing them from converting androgen into estrogen
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Notice: This product is only suitable for laboratory use, or the use of animals. It can not be used directly on the human body
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