Everolimus
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 100335

CAS#: 159351-69-6

Description: Everolimus, also known as RAD001, is a derivative of the natural macrocyclic lactone sirolimus with immunosuppressant and anti-angiogenic properties. In cells, everolimus binds to the immunophilin FK Binding Protein-12 (FKBP-12) to generate an immunosuppressive complex that binds to and inhibits the activation of the mammalian Target of Rapamycin (mTOR), a key regulatory kinase. Inhibition of mTOR activation results in the inhibition of T lymphocyte activation and proliferation associated with antigen and cytokine (IL-2, IL-4, and IL-15) stimulation and the inhibition of antibody production.


Price and Availability

Size
Price

10mg
USD 150
500mg
USD 1450
Size
Price

25mg
USD 250
1g
USD 2250
Size
Price

100mg
USD 650
5g
USD 4950

Everolimus, purity > 98%, is in stock. The same day shipping out after order is received. Note: the estimated shipping out time for order > 2g may be 2 weeks.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 100335
Name: Everolimus
CAS#: 159351-69-6
Chemical Formula: C53H83NO14
Exact Mass: 957.58136
Molecular Weight: 958.22
Elemental Analysis: C, 66.43; H, 8.73; N, 1.46; O, 23.38


Synonym: RAD001; RAD001; RAD 001.SDZ-RAD; Everolimus; Brand name Afinitor; Zortress; Certican; Zortress; Xience V.

IUPAC/Chemical Name: (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18- dihydroxy-12-{(1R)-2-[(1S,3R,4R)-4-(2hydroxyethoxy)-3-methoxycyclohexyl]-1-methylethyl}-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-aza-tricyclo[30.3.1.04,9]hexatriaconta16,24,26,28-tetraene-2,3,10,14,20-pentaone.

InChi Key: HKVAMNSJSFKALM-GKUWKFKPSA-N

InChi Code: InChI=1S/C53H83NO14/c1-32-16-12-11-13-17-33(2)44(63-8)30-40-21-19-38(7)53(62,68-40)50(59)51(60)54-23-15-14-18-41(54)52(61)67-45(35(4)28-39-20-22-43(66-25-24-55)46(29-39)64-9)31-42(56)34(3)27-37(6)48(58)49(65-10)47(57)36(5)26-32/h11-13,16-17,27,32,34-36,38-41,43-46,48-49,55,58,62H,14-15,18-26,28-31H2,1-10H3/b13-11+,16-12+,33-17+,37-27+/t32-,34-,35-,36-,38-,39+,40+,41+,43-,44+,45+,46-,48-,49+,53-/m1/s1

SMILES Code: O=C(C(N1CCCC[C@@]1([H])C(O[C@H]([C@H](C)C[C@H]2C[C@@H](OC)[C@H](OCCO)CC2)CC([C@H](C)/C=C(C)/[C@@H](O)[C@H]3OC)=O)=O)=O)[C@@](O4)(O)[C@H](C)CC[C@@]4([H])C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C3=O


Technical Data

Appearance:
White to off-white solid powder

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

Safety Data Sheet (MSDS):

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).

Harmonized System Code:
293490


Additional Information

Approved indication ( source: http://en.wikipedia.org/wiki/Everolimus ). Everolimus is approved for various conditions: (1). Advanced kidney cancer (approved in March 2009). (2). Prevention of organ rejection after renal transplant(April 2010. (3). Subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis (TS) in patients who are not suitable for surgical intervention (October 2010). (4). Progressive or metastatic pancreatic neuroendocrine tumors not surgically removable (May 2011).
 
AFINITOR is supplied as tablets for oral administration containing 5 mg and 10 mg of everolimus together with butylated hydroxytoluene, magnesium stearate, lactose monohydrate, hypromellose, crospovidone and lactose anhydrous as inactive ingredients.
   
According to http://en.wikipedia.org/wiki/Everolimus, As of October 2010, Phase III trials are under way in breast cancer, gastric cancer, hepatocellular carcinoma and lymphoma. Interim phase III trial results in 2011 show that adding Afinitor (everolimus) to exemestane therapy against advanced breast cancer can significantly improve progression-free survival compared with exemestane therapy alone.
 
 
Mechanism of action of Everolimus
Mechanism of action of Everolimus
In a similar fashion to other mTOR inhibitors its effect is solely on the mTORC1 protein and not on the mTORC2 protein. This can lead to a hyper-activation of the kinase AKT via inhibition on the mTORC1 negative feedback loop while not inhibiting the mTORC2 positive feedback to AKT. This AKT elevation can lead to longer survival in some cell types.
In a similar fashion to other mTOR inhibitors its effect is solely on the mTORC1 protein and not on the mTORC2 protein. This can lead to a hyper-activation of the kinase AKT via inhibition on the mTORC1 negative feedback loop while not inhibiting the mTORC2 positive feedback to AKT. This AKT elevation can lead to longer survival in some cell types.
 
 


References

1: Ganschow R, Pollok JM, Jankofsky M, Junge G. The role of everolimus in liver transplantation. Clin Exp Gastroenterol. 2014 Sep 2;7:329-43. doi: 10.2147/CEG.S41780. eCollection 2014. Review. PubMed PMID: 25214801; PubMed Central PMCID: PMC4159129.

2: Dorris JR 3rd, Jones S. Everolimus in Breast Cancer: The Role of the Pharmacist. Ann Pharmacother. 2014 Jul 9;48(9):1194-1201. [Epub ahead of print] Review. PubMed PMID: 25007922.

3: Ng VC, Johnson JJ, Cuellar S. Targeting the mammalian target of rapamycin pathway with everolimus: Implications for the management of metastatic breast cancer. J Oncol Pharm Pract. 2014 Jun 25. pii: 1078155214540732. [Epub ahead of print] Review. PubMed PMID: 24964967.

4: Hasskarl J. Everolimus. Recent Results Cancer Res. 2014;201:373-92. doi: 10.1007/978-3-642-54490-3_23. Review. PubMed PMID: 24756805.

5: 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.

6: Aapro M, Andre F, Blackwell K, Calvo E, Jahanzeb M, Papazisis K, Porta C, Pritchard K, Ravaud A. Adverse event management in patients with advanced cancer receiving oral everolimus: focus on breast cancer. Ann Oncol. 2014 Apr;25(4):763-73. doi: 10.1093/annonc/mdu021. Review. PubMed PMID: 24667713.

7: Lombard-Bohas C, Cariou B, Vergès B, Coriat R, N'guyen T, François E, Hammel P, Niccoli P, Hentic O. [Management of metabolic disorders induced by everolimus in patients with differentiated neuroendocrine tumors: expert proposals]. Bull Cancer. 2014 Feb;101(2):175-83. doi: 10.1684/bdc.2014.1887. Review. French. PubMed PMID: 24557872.

8: Gnant M, Greil R, Hubalek M, Steger G. Everolimus in postmenopausal, hormone receptor-positive advanced breast cancer: summary and results of an austrian expert panel discussion. Breast Care (Basel). 2013 Aug;8(4):293-9. doi: 10.1159/000354121. Review. PubMed PMID: 24415983; PubMed Central PMCID: PMC3808223.

9: Yamanaka K, Petrulionis M, Lin S, Gao C, Galli U, Richter S, Winkler S, Houben P, Schultze D, Hatano E, Schemmer P. Therapeutic potential and adverse events of everolimus for treatment of hepatocellular carcinoma - systematic review and meta-analysis. Cancer Med. 2013 Dec;2(6):862-71. doi: 10.1002/cam4.150. Epub 2013 Oct 22. Review. PubMed PMID: 24403259; PubMed Central PMCID: PMC3892390.

10: Hirt SW, Bara C, Barten MJ, Deuse T, Doesch AO, Kaczmarek I, Schulz U, Stypmann J, Haneya A, Lehmkuhl HB. Everolimus in heart transplantation: an update. J Transplant. 2013;2013:683964. doi: 10.1155/2013/683964. Epub 2013 Dec 5. Review. PubMed PMID: 24382994; PubMed Central PMCID: PMC3870122.