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Purity: ≥98%
Exemestane (formerly also known as FCE24304, PNU155971; FCE 24304; EXE), a drug used in ER-positive breast cancer, is a synthetic and potent aromatase inhibitor, which inhibits human placental and rat ovarian aromatase with IC50 of 30 nM and 40 nM, respectively. Exemestane binds irreversibly to and inhibits the enzyme aromatase, thereby blocking the conversion of cholesterol to pregnenolone and the peripheral aromatization of androgenic precursors into estrogens. Structurally similar to androstenedione, exemestane might have a big impact on androgenic effect.
Targets |
Aromatase (IC50s = 30 nM)
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ln Vitro |
Exemestane dramatically boosts the number of cells in hFOB, Saos-2 cells (1-1000 nM; 72 h) [2]. Exemestane (72 h) stimulates the expression of MYBL2, OSTM1, HOXD11, ADCYAP1R1, and glypican 2 in hFOB cells and boosts alkaline phosphatase activity in Saos-2 and hFOB cells [2]. With a Ki of 4.3 nM, exemestane competitively inhibits and inactivates human placental aromatase in a time-dependent manner. With an IC50 of 0.9 μM, exemestane substitutes [3H]5α-dihydrotestosterone in the rat prostate androgen receptor [1].
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ln Vivo |
Treatment with exemestane (20–100 mg/kg; intramuscular injection; once weekly; for 16 weeks) resulted in significant increases in trabecular bone volume, fifth lumbar vertebra compressive strength, femoral flexural strength, and lumbar and femoral BMD. Exemestane considerably lowers the elevations in serum osteocalcin and pyridinoline that are brought on by ovariectomy. Serum cholesterol and LDL cholesterol are markedly lowered with exemestane [3]. Rats with mammary tumors produced by 7,12-dimethylbenzanthracene (DMBA) show 26% complete (CR) and 18% partial (PR) tumor regression when exposed to exemestane (20 mg/kg/day) subcutaneously [4].
When given orally for 7 days in castrated and testosterone (Silastic implants) supplemented rats, the new compounds were very effective in reducing prostate growth. At a dose of 0.3 mg/kg/day inhibitions of 42, 36 and 41% were caused by FCE 28260, FCE 28175 and FCE 27837, respectively.[1] |
Enzyme Assay |
Inhibitors of aromatase and 5 alpha-reductase may be of use for the therapy of postmenopausal breast cancer and benign prostatic hyperplasia, respectively. FCE 27993 is a novel steroidal irreversible aromatase inhibitor structurally related to exemestane (FCE 24304). The compound was found to be a very potent competitive inhibitor of human placental aromatase, with a Ki of 7.2 nM (4.3 nM for exemestane). In preincubation studies with placental aromatase FCE 27993, like exemestane, was found to cause time-dependent inhibition with a higher rate of inactivation (t1/2 4.5 vs 15.1 min) and a similar Ki(inact) (56 vs 66 nM). The compound was found to have a very low binding affinity to the androgen receptor (RBA 0.09% of dihydrotestosterone) and, in contrast to exemestane, no androgenic activity up to 100 mg/kg/day s.c. in immature castrated rats. Among a series of novel 4-azasteroids with fluoro-substituted-17 beta-amidic side chains, three compounds, namely FCE 28260, FCE 28175 and FCE 27837, were identified as potent in vitro and in vivo inhibitors of prostatic 5 alpha-reductase. Their IC50 values were found to be 16, 38 and 51 nM for the inhibition of the human enzyme, and 15, 20 and 60 nM for the inhibition of the rat enzyme, respectively[1].
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Cell Assay |
Cell Viability Assay[2]
Cell Types: hFOB, Saos-2 cells Tested Concentrations: 1 nM, 10 nM, 100 nM, 1000 nM Incubation Duration: 72 hrs (hours) Experimental Results: Induced cell proliferation. |
Animal Protocol |
Animal/Disease Models: Female Sprague Dawley rats (10-month-old) bearing ovariectomy [3]
Doses: 20 mg/kg, 50 mg/kg, or 100 mg/kg Route of Administration: intramuscular (im) injection; once weekly; for 16 weeks Experimental Results: Dramatically increased the lumbar vertebral and femoral BMD, bending strength of the femur, compressive strength of the fifth lumbar vertebra, and trabecular bone volume. |
References |
[1]. Di Salle, E., et al., Novel aromatase and 5 alpha-reductase inhibitors. J Steroid Biochem Mol Biol, 1994. 49(4-6): p. 289-94.
[2]. Miki, Y, et al. Effects of aromatase inhibitors on human osteoblast and osteoblast-like cells: a possible androgenic bone protective effects induced by exemestane. Bone. 2004 Sep 1;10(17):5717-23. [3]. Goss, P.E., et al., Effects of the steroidal aromatase inhibitor exemestane and the nonsteroidal aromatase inhibitor letrozole on bone and lipid metabolism in ovariectomized rats. Clin Cancer Res, 2004. 10(17): p. 5717-23. [4]. Zaccheo, T., D. Giudici, and E. Di Salle, Inhibitory effect of combined treatment with the aromatase inhibitor exemestane and tamoxifen on DMBA-induced mammary tumors in rats. J Steroid Biochem Mol Biol, 1993. 44(4-6): p. 677-80. |
Additional Infomation |
Purpose: Exemestane (EXE) and letrozole (LET) are third-generation aromatase inhibitors currently prescribed for postmenopausal hormone-dependent breast cancer. The impact on end organs of estrogen depletion in menopausal women is of significant clinical importance. We studied the effects of EXE, its principal metabolite, 17-hydroexemestane (17-H-EXE), and LET on bone and lipid metabolism in ovariectomized (OVX) rats.[2]
Experimental design: OVX rats were treated by weekly intramuscular injection for 16 weeks with 20, 50, and 100 mg/kg EXE, 20 mg/kg 17-H-EXE, and daily oral gavage of 1 mg/kg LET. At the end of the treatment period, bone mineral density (BMD), the bone resorption marker serum pyridinoline, the bone formation marker serum osteocalcin, bone mechanical properties, histomorphometry, and serum lipid concentrations were determined.[2] Results: Lumbar vertebral and femoral BMD, bending strength of the femur, compressive strength of the fifth lumbar vertebra, and trabecular bone volume were significantly higher in OVX animals given EXE and 17-H-EXE than in OVX controls. EXE and 17-H-EXE significantly reduced an ovariectomy-induced increase in serum pyridinoline and serum osteocalcin. EXE and 17-H-EXE given to OVX rats caused significant reductions of serum cholesterol and low-density lipoprotein cholesterol. In contrast, OVX rats treated with LET had BMD, bone biomarkers, mechanical failure properties, and lipid levels similar to those of OVX controls.[2] Conclusions: EXE and 17-H-EXE significantly prevent bone loss, enhance bone mechanical strength, and lower serum cholesterol and low-density lipoprotein levels in OVX rats. These protective effects on end-organ function are not seen with the nonsteroidal inhibitor LET. Exemestane is 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 breast cancer. It has a role as an EC 1.14.14.14 (aromatase) inhibitor, an antineoplastic agent, an environmental contaminant and a xenobiotic. It is a 17-oxo steroid and a 3-oxo-Delta(1),Delta(4)-steroid. It derives from a hydride of an androstane. Exemestane is an oral steroidal aromatase inhibitor used in the adjuvant treatment of hormonally-responsive (also called hormone-receptor-positive, estrogen-responsive) breast cancer in postmenopausal women. It irreversibly binds to the active site of the enzyme resulting in permanent inhibition. Exemestane is an Aromatase Inhibitor. The mechanism of action of exemestane is as an Aromatase Inhibitor. Exemestane is a steroidal inhibitor of aromatase which effectively blocks estrogen synthesis in postmenopausal women and is used as therapy of estrogen receptor positive breast cancer, usually after resection and after failure of tamoxifen. Exemestane has been associated with a low rate of serum enzyme elevations during therapy and rare instances of clinically apparent liver injury. Exemestane is an irreversible steroidal aromatase inhibitor, with antiestrogen and antineoplastic activities. Upon oral administration, exemestane binds irreversibly to and inhibits the enzyme aromatase, thereby blocking the peripheral aromatization of androgens, including androstenedione and testosterone, to estrogens. This lowers estrogen levels in the blood circulation. |
Molecular Formula |
C20H24O2
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Molecular Weight |
296.4
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Exact Mass |
296.1776
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Elemental Analysis |
C, 81.04; H, 8.16; O, 10.80
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CAS # |
107868-30-4
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Related CAS # |
Exemestane (Standard);107868-30-4;Exemestane-d2;Exemestane-13C3;Exemestane-d3
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PubChem CID |
60198
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Appearance |
Typically exists as white to off-white solids at room temperature
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Density |
1.1±0.1 g/cm3
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Boiling Point |
453.7±45.0 °C at 760 mmHg
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Melting Point |
155.13°C
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Flash Point |
169.0±25.7 °C
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Vapour Pressure |
0.0±1.1 mmHg at 25°C
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Index of Refraction |
1.572
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LogP |
3.11
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tPSA |
34.14
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SMILES |
O=C(C=C1C(C[C@@]2([H])[C@]3([H])CC4)=C)C=C[C@]1(C)[C@@]2([H])CC[C@]3(C)C4=O
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InChi Key |
BFYIZQONLCFLEV-DAELLWKTSA-N
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InChi Code |
InChI=1S/C20H24O2/c1-12-10-14-15-4-5-18(22)20(15,3)9-7-16(14)19(2)8-6-13(21)11-17(12)19/h6,8,11,14-16H,1,4-5,7,9-10H2,2-3H3/t14-,15-,16-,19+,20-/m0/s1
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Chemical Name |
(8R,9S,10R,13S,14S)-10,13-dimethyl-6-methylene-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a]phenanthrene-3,17(6H)-dione.
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Synonyms |
FCE24304, PNU155971; PNU155971; PNU-155971; PNU 155971; FCE24304; FCE-24304; FCE 24304; Exemestane; US trade name: Aromasin.
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.43 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (8.43 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (8.43 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 3.3738 mL | 16.8691 mL | 33.7382 mL | |
5 mM | 0.6748 mL | 3.3738 mL | 6.7476 mL | |
10 mM | 0.3374 mL | 1.6869 mL | 3.3738 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.