Everolimus | RAD-001 | CAS#15951-69-6

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.

Chemical Structure

Everolimus

CAS# 159351-69-6

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 100335
Name: Everolimus
CAS#: 159351-69-6
Chemical Formula: C53H83NO14
Exact Mass: 957.58
Molecular Weight: 958.220
Elemental Analysis: C, 66.43; H, 8.73; N, 1.46; O, 23.38

Price and Availability

Size	Price	Availability
10mg	USD 90	Ready to ship
25mg	USD 150	Ready to ship
50mg	USD 250	Ready to ship
100mg	USD 450	Ready to ship
200mg	USD 750	Ready to ship
500mg	USD 1650	Ready to ship
1g	USD 2950	Ready to ship
2g	USD 5250	Ready to ship
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: RAD-001; 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

Appearance: White to off-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

More Info: 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.

Product Data:

Product Data

Certificate of Analysis:

View CoA: current batch, Lot#A9T07K18

QC Data:

View QC data: current batch, Lot#A9T07K18

Safety Data Sheet (SDS):

View Safety Data Sheet (SDS)

Instruction:

View handling instruction

Biological target:	Everolimus (RAD001) is a potent and selective mTOR1 inhibitor that binds to FKBP-12 to generate an immunosuppressive complex.
In vitro activity:	Significant differences between TWIST1 RQs normalized to the three controls were observed in the RKO-AS45-1 and BT-549 cell lines following everolimus treatment (Fig. 1B). TWIST1 was downregulated in RKO-AS45-1 compared with untreated BT-549 and WI-26 VA4 cells, but upregulated compared with untreated RKO-AS45-1 cells. In BT-549 cells, TWIST1 was upregulated compared with all three normalization controls. In TOV-21G cells, TWIST1 appeared to be downregulated compared with the control, and no statistical differences were observed between the analyzed groups. Reference: Oncol Lett. 2020 Nov; 20(5): 158. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471649/
In vivo activity:	To reveal the underlying mechanism of blocking DCIS invasion by mTOR inhibition, this study investigated the effects of mTOR inhibitor on MMP9, a classic invasion-driver protein. As shown in Fig. 6A, everolimus treatment not only inhibited the phosphorylation of P70S6K1 (p-P70S6K1), an mTOR substrate, but also decreased MMP9 protein levels in SUM225 cells. Similarly, the 1-week everolimus treatment also reduced p-P70S6K1 and MMP9 levels in the mammary tumors from the MMTV/neu mice in vivo (Fig. 6B). In addition, IHC assays also revealed reduction of MMP9 expression in both SUM225-MIND and MMTV/neu mouse mammary tissues after the treatment with everolimus in vivo (Fig. 6C and D). Reference: Clin Cancer Res. 2020 Mar 15;26(6):1486-1496. https://clincancerres.aacrjournals.org/content/26/6/1486.long

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMSO	97.9	102.18
	Ethanol	97.9	102.18

Preparing Stock Solutions

The following data is based on the product molecular weight 958.22 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.

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. Gonçalves BÔP, De Andrade WP, Da Conceição Braga L, Fialho SL, Silva LM. Epithelial-to-mesenchymal transition markers are differentially expressed in epithelial cancer cell lines after everolimus treatment. Oncol Lett. 2020 Nov;20(5):158. doi: 10.3892/ol.2020.12019. Epub 2020 Aug 25. PMID: 32934726; PMCID: PMC7471649. 2. Ashley D, Hernandez J, Cao R, To K, Yegiazaryan A, Abrahem R, Nguyen T, Owens J, Lambros M, Subbian S, Venketaraman V. Antimycobacterial Effects of Everolimus in a Human Granuloma Model. J Clin Med. 2020 Jun 29;9(7):2043. doi: 10.3390/jcm9072043. PMID: 32610643; PMCID: PMC7409120. 3. Chang GR, Hou PH, Wang CM, Wu CF, Su HK, Liao HJ, Chen TP. Chronic everolimus treatment of high-fat diet mice leads to a reduction in obesity but impaired glucose tolerance. Pharmacol Res Perspect. 2021 Apr;9(2):e00732. doi: 10.1002/prp2.732. PMID: 33715287; PMCID: PMC7955951. 4. Chen G, Ding XF, Pressley K, Bouamar H, Wang B, Zheng G, Broome LE, Nazarullah A, Brenner AJ, Kaklamani V, Jatoi I, Sun LZ. Everolimus Inhibits the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer Via Downregulation of MMP9 Expression. Clin Cancer Res. 2020 Mar 15;26(6):1486-1496. doi: 10.1158/1078-0432.CCR-19-2478. Epub 2019 Dec 23. PMID: 31871301.
In vitro protocol:	1. Gonçalves BÔP, De Andrade WP, Da Conceição Braga L, Fialho SL, Silva LM. Epithelial-to-mesenchymal transition markers are differentially expressed in epithelial cancer cell lines after everolimus treatment. Oncol Lett. 2020 Nov;20(5):158. doi: 10.3892/ol.2020.12019. Epub 2020 Aug 25. PMID: 32934726; PMCID: PMC7471649. 2. Ashley D, Hernandez J, Cao R, To K, Yegiazaryan A, Abrahem R, Nguyen T, Owens J, Lambros M, Subbian S, Venketaraman V. Antimycobacterial Effects of Everolimus in a Human Granuloma Model. J Clin Med. 2020 Jun 29;9(7):2043. doi: 10.3390/jcm9072043. PMID: 32610643; PMCID: PMC7409120.
In vivo protocol:	1. Chang GR, Hou PH, Wang CM, Wu CF, Su HK, Liao HJ, Chen TP. Chronic everolimus treatment of high-fat diet mice leads to a reduction in obesity but impaired glucose tolerance. Pharmacol Res Perspect. 2021 Apr;9(2):e00732. doi: 10.1002/prp2.732. PMID: 33715287; PMCID: PMC7955951. 2. Chen G, Ding XF, Pressley K, Bouamar H, Wang B, Zheng G, Broome LE, Nazarullah A, Brenner AJ, Kaklamani V, Jatoi I, Sun LZ. Everolimus Inhibits the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer Via Downregulation of MMP9 Expression. Clin Cancer Res. 2020 Mar 15;26(6):1486-1496. doi: 10.1158/1078-0432.CCR-19-2478. Epub 2019 Dec 23. PMID: 31871301.

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1: Hasskarl J. Everolimus. Recent Results Cancer Res. 2018;211:101-123. doi: 10.1007/978-3-319-91442-8_8. PMID: 30069763.

2: Pascual J, Berger SP, Witzke O, Tedesco H, Mulgaonkar S, Qazi Y, Chadban S, Oppenheimer F, Sommerer C, Oberbauer R, Watarai Y, Legendre C, Citterio F, Henry M, Srinivas TR, Luo WL, Marti A, Bernhardt P, Vincenti F; TRANSFORM Investigators. Everolimus with Reduced Calcineurin Inhibitor Exposure in Renal Transplantation. J Am Soc Nephrol. 2018 Jul;29(7):1979-1991. doi: 10.1681/ASN.2018010009. Epub 2018 May 11. PMID: 29752413; PMCID: PMC6050928.

3: Lee L, Ito T, Jensen RT. Everolimus in the treatment of neuroendocrine tumors: efficacy, side-effects, resistance, and factors affecting its place in the treatment sequence. Expert Opin Pharmacother. 2018 Jun;19(8):909-928. doi: 10.1080/14656566.2018.1476492. Epub 2018 May 24. PMID: 29757017; PMCID: PMC6064188.

4: Mousa OY, Keaveny AP. Everolimus: Longer-Term CERTITUDE. Liver Transpl. 2019 Dec;25(12):1745-1746. doi: 10.1002/lt.25659. PMID: 31606937.

5: Bevacqua M, Baldo F, Pastore S, Valencic E, Tommasini A, Maestro A, Rabusin M, Arbo A, Barbi E. Off-Label Use of Sirolimus and Everolimus in a Pediatric Center: A Case Series and Review of the Literature. Paediatr Drugs. 2019 Jun;21(3):185-193. doi: 10.1007/s40272-019-00337-7. PMID: 31124053.

6: Kobayashi H. Everolimus-Eluting Stent-induced Pneumonitis. Am J Respir Crit Care Med. 2022 Mar 15;205(6):12-13. doi: 10.1164/rccm.202103-0565IM. PMID: 34491881.

7: Witzke O, Sommerer C, Arns W. Everolimus immunosuppression in kidney transplantation: What is the optimal strategy? Transplant Rev (Orlando). 2016 Jan;30(1):3-12. doi: 10.1016/j.trre.2015.09.001. Epub 2015 Sep 18. PMID: 26603484.

8: Tang CY, Shen A, Wei XF, Li QD, Liu R, Deng HJ, Wu YZ, Wu ZJ. Everolimus in de novo liver transplant recipients: a systematic review. Hepatobiliary Pancreat Dis Int. 2015 Oct;14(5):461-9. doi: 10.1016/s1499-3872(15)60419-2. PMID: 26459721.

9: Rodríguez-Arias JJ, Ortega-Paz L, Brugaletta S. Durable polymer everolimus- eluting stents: history, current status and future prospects. Expert Rev Med Devices. 2020 Jul;17(7):671-682. doi: 10.1080/17434440.2020.1784005. Epub 2020 Jun 30. PMID: 32543934.

10: French JA, Lawson JA, Yapici Z, Ikeda H, Polster T, Nabbout R, Curatolo P, de Vries PJ, Dlugos DJ, Berkowitz N, Voi M, Peyrard S, Pelov D, Franz DN. Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): a phase 3, randomised, double- blind, placebo-controlled study. Lancet. 2016 Oct 29;388(10056):2153-2163. doi: 10.1016/S0140-6736(16)31419-2. Epub 2016 Sep 6. PMID: 27613521.

11: Nye L, Khan SA. Everolimus for Estrogen Receptor-negative Breast Cancer Prevention: A Journey Begun? Cancer Prev Res (Phila). 2022 Dec 1;15(12):787-789. doi: 10.1158/1940-6207.CAPR-22-0419. PMID: 36453053.

12: van Gelder T, Fischer L, Shihab F, Shipkova M. Optimizing everolimus exposure when combined with calcineurin inhibitors in solid organ transplantation. Transplant Rev (Orlando). 2017 Jul;31(3):151-157. doi: 10.1016/j.trre.2017.02.007. Epub 2017 Feb 27. PMID: 28279567.

13: De Simone P, Bronzoni J, Martinelli C. Everolimus versus mycophenolate mofetil in liver transplantation: every improvement in renal function matters. Rev Esp Enferm Dig. 2022 Jun;114(6):312-313. doi: 10.17235/reed.2022.8902/2022. PMID: 35545915.

14: Falkowski S, Woillard JB. Therapeutic Drug Monitoring of Everolimus in Oncology: Evidences and Perspectives. Ther Drug Monit. 2019 Oct;41(5):568-574. doi: 10.1097/FTD.0000000000000628. PMID: 30913132.

15: Geng W, Cao M, Dong K, An J, Gao H. SHOC2 mediates the drug-resistance of triple-negative breast cancer cells to everolimus. Cancer Biol Ther. 2023 Dec 31;24(1):2206362. doi: 10.1080/15384047.2023.2206362. PMID: 37170083; PMCID: PMC10177683.

16: Gallo M, Malandrino P, Fanciulli G, Rota F, Faggiano A, Colao A; NIKE Group. Everolimus as first line therapy for pancreatic neuroendocrine tumours: current knowledge and future perspectives. J Cancer Res Clin Oncol. 2017 Jul;143(7):1209-1224. doi: 10.1007/s00432-017-2407-5. Epub 2017 Apr 12. PMID: 28405826.

17: Rubín Suárez A, Bilbao Aguirre I, Fernández-Castroagudin J, Pons Miñano JA, Salcedo Plaza M, Varo Pérez E, Prieto Castillo M. Recommendations of everolimus use in liver transplant. Gastroenterol Hepatol. 2017 Nov;40(9):629-640. English, Spanish. doi: 10.1016/j.gastrohep.2017.05.008. Epub 2017 Jul 23. PMID: 28743539.

18: Dumortier J, Dharancy S, Calmus Y, Duvoux C, Durand F, Salamé E, Saliba F. Use of everolimus in liver transplantation: The French experience. Transplant Rev (Orlando). 2016 Jul;30(3):161-70. doi: 10.1016/j.trre.2015.12.003. Epub 2016 Mar 18. PMID: 27083870.

19: Kazzaz F, O'Connell OJ, Vial MR, Stewart J, Grosu HB. Everolimus-induced Chylous Effusion. Am J Respir Crit Care Med. 2018 Jul 1;198(1):120-122. doi: 10.1164/rccm.201707-1438IM. PMID: 29630393.

20: Pronzato P. Role of everolimus in the treatment of metastatic HER2-negative/HR-positive breast cancer. Future Oncol. 2017 Jul;13(16):1371-1384. doi: 10.2217/fon-2017-0098. Epub 2017 Apr 26. PMID: 28443700.

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