Exemestane
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MedKoo CAT#: 100340

CAS#: 107868-30-4

Description: Exemestane is a synthetic androgen analogue. 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.


Chemical Structure

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Exemestane
CAS# 107868-30-4

Theoretical Analysis

MedKoo Cat#: 100340
Name: Exemestane
CAS#: 107868-30-4
Chemical Formula: C20H24O2
Exact Mass: 296.17763
Molecular Weight: 296.4
Elemental Analysis: C, 81.04; H, 8.16; O, 10.80

Price and Availability

Size Price Availability Quantity
200.0mg USD 90.0 Same day
500.0mg USD 150.0 Same day
1.0g USD 250.0 Same day
2.0g USD 450.0 Same day
5.0g USD 750.0 Same day
10.0g USD 1250.0 Same day
20.0g USD 1950.0 Same day
50.0g USD 4250.0 Same day
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Synonym: PNU155971; PNU-155971; PNU 155971; FCE24304; FCE-24304; FCE 24304; Exemestane; US brand name: Aromasin.

IUPAC/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.

InChi Key: BFYIZQONLCFLEV-DAELLWKTSA-N

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

SMILES Code: 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

Appearance: white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Exemestane (FCE24304, PNU155971) is an aromatase inhibitor, inhibits human placental and rat ovarian aromatase with IC50 of 30 nM and 40 nM, respectively.
In vitro activity: As shown in Fig. 4B, exemestane inhibited aromatase in MCF-7aro cells in a time-dependent manner. Based on previous knowledge and findings from this study, as shown in Scheme 1 , the interaction between exemestane and aromatase can be divided into three steps. Step 1 is the reversible step when exemestane binds to aromatase with a Ki of 26 nmol/L. At step 2, exemestane is converted into an intermediate, through a yet unknown process, and results in an irreversible inactivation of the enzyme. The t1/2 of this process is ∼13.9 minutes. At step 3, a degradation of aromatase by proteasome occurs after the irreversible inactivation step. We have found that in vitro incubation of exemestane with purified aromatase had no effect on aromatase protein stability. Following the exemestane treatment of MCF-7aro cells, the t1/2 of aromatase protein is reduced by 50% or more. We have determined that exemestane, at 200 nmol/L, decreases aromatase t1/2 to 12.5 hours from 28.2 hours in untreated cells. In addition, exemestane treatment did not cause significant changes of aromatase mRNA levels. Therefore, exemestane is a unique AI that can also destabilize aromatase protein. Reference: Cancer Res. 2006 Nov 1;66(21):10281-6. https://cancerres.aacrjournals.org/content/66/21/10281.long
In vivo activity: The effect of EXE on liver injury and fibrosis were assessed in two hepatic fibrosis rat models, which were induced by either carbon tetrachloride (CCl4) or bile duct ligation (BDL). The influence of EXE treatment on activation and proliferation of primary rat hepatic stellate cells (HSCs) was observed in vitro. The results showed that EXE attenuated the liver fibrosis by decreasing the collagen deposition and α-SMA expression in vivo and inhibited the activation and proliferation of primary rat HSCs in vitro. Additionally, EXE promoted the secretion of antifibrotic and anti-inflammatory cytokine IL-10 in vivo and in HSC-T6 culture media. In conclusion, our findings reveal a new function of EXE on hepatic fibrosis and prompted its latent application in liver fibrotic-related disease. Reference: J Immunol Res. 2017;2017:3072745. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29464186/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 54.0 182.19
Ethanol 21.0 70.85

Preparing Stock Solutions

The following data is based on the product molecular weight 296.4 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Wang X, Chen S. Aromatase destabilizer: novel action of exemestane, a food and drug administration-approved aromatase inhibitor. Cancer Res. 2006 Nov 1;66(21):10281-6. doi: 10.1158/0008-5472.CAN-06-2134. PMID: 17079446. 2. Jayapal JJ, Dhanaraj S. Exemestane loaded alginate nanoparticles for cancer treatment: Formulation and in vitro evaluation. Int J Biol Macromol. 2017 Dec;105(Pt 1):416-421. doi: 10.1016/j.ijbiomac.2017.07.064. Epub 2017 Jul 13. PMID: 28711612. 3. Wang YH, Li RK, Fu Y, Li J, Yang XM, Zhang YL, Zhu L, Yang Q, Gu JR, Xing X, Zhang ZG. Exemestane Attenuates Hepatic Fibrosis in Rats by Inhibiting Activation of Hepatic Stellate Cells and Promoting the Secretion of Interleukin 10. J Immunol Res. 2017;2017:3072745. doi: 10.1155/2017/3072745. Epub 2017 Dec 10. PMID: 29464186; PMCID: PMC5804406.
In vitro protocol: 1. Wang X, Chen S. Aromatase destabilizer: novel action of exemestane, a food and drug administration-approved aromatase inhibitor. Cancer Res. 2006 Nov 1;66(21):10281-6. doi: 10.1158/0008-5472.CAN-06-2134. PMID: 17079446. 2. Jayapal JJ, Dhanaraj S. Exemestane loaded alginate nanoparticles for cancer treatment: Formulation and in vitro evaluation. Int J Biol Macromol. 2017 Dec;105(Pt 1):416-421. doi: 10.1016/j.ijbiomac.2017.07.064. Epub 2017 Jul 13. PMID: 28711612.
In vivo protocol: 1. Wang YH, Li RK, Fu Y, Li J, Yang XM, Zhang YL, Zhu L, Yang Q, Gu JR, Xing X, Zhang ZG. Exemestane Attenuates Hepatic Fibrosis in Rats by Inhibiting Activation of Hepatic Stellate Cells and Promoting the Secretion of Interleukin 10. J Immunol Res. 2017;2017:3072745. doi: 10.1155/2017/3072745. Epub 2017 Dec 10. PMID: 29464186; PMCID: PMC5804406.

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1: Gilabert M, Launay S, Gonçalves A. [Exemestane-everolimus in HER2-negative, hormonal receptor-positive, post-menopausal metastatic breast cancer with resistance to non-steroidal aromatase inhibitor: a new option]. Bull Cancer. 2014 Mar;101(3):325-33. doi: 10.1684/bdc.2014.1910. Review. French. PubMed PMID: 24691195.

2: Van Asten K, Neven P, Lintermans A, Wildiers H, Paridaens R. Aromatase inhibitors in the breast cancer clinic: focus on exemestane. Endocr Relat Cancer. 2014 Jan 16;21(1):R31-49. doi: 10.1530/ERC-13-0269. Print 2014 Feb. Review. PubMed PMID: 24434719.

3: Dunn BK, Cazzaniga M, DeCensi A. Exemestane: one part of the chemopreventive spectrum for ER-positive breast cancer. Breast. 2013 Jun;22(3):225-37. doi: 10.1016/j.breast.2013.02.015. Epub 2013 Mar 25. Review. PubMed PMID: 23535509.

4: Dhillon S. Everolimus in combination with exemestane: a review of its use in the treatment of patients with postmenopausal hormone receptor-positive, HER2-negative advanced breast cancer. Drugs. 2013 Apr;73(5):475-85. doi: 10.1007/s40265-013-0034-2. Review. PubMed PMID: 23529824.

5: Decensi A, Dunn BK, Puntoni M, Gennari A, Ford LG. Exemestane for breast cancer prevention: a critical shift? Cancer Discov. 2012 Jan;2(1):25-40. doi: 10.1158/2159-8290.CD-11-0248. Review. PubMed PMID: 22585166; PubMed Central PMCID: PMC3354700.

6: Santoro S, Santini M, Pepe C, Tognetti E, Cortelazzi C, Ficarelli E, De Panfilis G. Aromatase inhibitor-induced skin adverse reactions: exemestane-related cutaneous vasculitis. J Eur Acad Dermatol Venereol. 2011 May;25(5):596-8. doi: 10.1111/j.1468-3083.2010.03803.x. Review. PubMed PMID: 21492245.

7: Lintermans A, Neven P, Paridaens R. Drug safety evaluation of exemestane. Expert Opin Drug Saf. 2011 May;10(3):473-87. doi: 10.1517/14740338.2011.567264. Epub 2011 Mar 24. Review. PubMed PMID: 21428848.

8: Bertelli G, Gangadhara S. Exemestane in postmenopausal women with early or advanced breast cancer: a review. Expert Opin Pharmacother. 2010 Aug;11(11):1933-42. doi: 10.1517/14656566.2010.495945. Review. PubMed PMID: 20569090.

9: Macpherson IR, Lindsay C, Canney P. Adjuvant treatment of breast cancer in postmenopausal women: role of exemestane. Breast Cancer (Dove Med Press). 2010 Oct 14;2:59-70. doi: 10.2147/BCTT.S11835. Review. PubMed PMID: 24367167; PubMed Central PMCID: PMC3846455.

10: Glück S. Exemestane as first-line therapy in postmenopausal women with recurrent or metastatic breast cancer. Am J Clin Oncol. 2010 Jun;33(3):314-9. doi: 10.1097/COC.0b013e31819fdf9b. Review. PubMed PMID: 19730353.



Additional Information

DRUG DESCRIPTION
AROMASIN® Tablets for oral administration contain 25 mg of exemestane, an irreversible, steroidal aromatase inactivator. Exemestane is chemically described as 6-methylenandrosta-1,4-diene-3,17-dione. Its molecular formula is C20H24O2. The active ingredient is a white to slightly yellow crystalline powder with a molecular weight of 296.41. Exemestane is freely soluble in N, N-dimethylformamide, soluble in methanol, and practically insoluble in water. Each AROMASIN Tablet contains the following inactive ingredients: mannitol, crospovidone, polysorbate 80, hypromellose, colloidal silicon dioxide, microcrystalline cellulose, sodium starch glycolate, magnesium stearate, simethicone, polyethylene glycol 6000, sucrose, magnesium carbonate, titanium dioxide, methylparaben, and polyvinyl alcohol.
 
 
Mechanism of Action
Mechanism of Action
Breast cancer cell growth may be estrogen-dependent. Aromatase is the principal enzyme that converts androgens to estrogens both in pre- and postmenopausal women. While the main source of estrogen (primarily estradiol) is the ovary in premenopausal women, the principal source of circulating estrogens in postmenopausal women is from conversion of adrenal and ovarian androgens (androstenedione and testosterone) to estrogens (estrone and estradiol) by the aromatase enzyme in peripheral tissues. Estrogen deprivation through aromatase inhibition is an effective and selective treatment for some postmenopausal patients with hormone-dependent breast cancer. Exemestane is an irreversible, steroidal aromatase inactivator, structurally related to the natural substrate 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.” Exemestane significantly lowers circulating estrogen concentrations in postmenopausal women, but has no detectable effect on adrenal biosynthesis of corticosteroids or aldosterone. Exemestane has no effect on other enzymes involved in the steroidogenic pathway up to a concentration at least 600 times higher than that inhibiting the aromatase enzyme.
Breast cancer cell growth may be estrogen-dependent. Aromatase is the principal enzyme that converts androgens to estrogens both in pre- and postmenopausal women. While the main source of estrogen (primarily estradiol) is the ovary in premenopausal women, the principal source of circulating estrogens in postmenopausal women is from conversion of adrenal and ovarian androgens (androstenedione and testosterone) to estrogens (estrone and estradiol) by the aromatase enzyme in peripheral tissues. Estrogen deprivation through aromatase inhibition is an effective and selective treatment for some postmenopausal patients with hormone-dependent breast cancer. Exemestane is an irreversible, steroidal aromatase inactivator, structurally related to the natural substrate 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.” Exemestane significantly lowers circulating estrogen concentrations in postmenopausal women, but has no detectable effect on adrenal biosynthesis of corticosteroids or aldosterone. Exemestane has no effect on other enzymes involved in the steroidogenic pathway up to a concentration at least 600 times higher than that inhibiting the aromatase enzyme.