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

MedKoo Cat#: 100335 | Name: Everolimus

Description:

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

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

Theoretical Analysis

MedKoo Cat#: 100335

Name: Everolimus

CAS#: 159351-69-6

Chemical Formula: C53H83NO14

Exact Mass: 957.5814

Molecular Weight: 958.22

Elemental Analysis: C, 66.43; H, 8.73; N, 1.46; O, 23.38

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 750.00	Ready to ship
500mg	USD 1,650.00	Ready to ship
1g	USD 2,950.00	Ready to ship
2g	USD 5,250.00	Ready to ship

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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

	Solvent	mg/mL	mM
Solubility
	DMSO	97.9	102.18
	Ethanol	97.9	102.18

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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:

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.

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.