Back to ChemicalBook Home--->CAS DataBase List--->159351-69-6

159351-69-6

159351-69-6 Structure

159351-69-6 Structure
IdentificationBack Directory
[Name]

Everolimus
[CAS]

159351-69-6
[Synonyms]

SDZRAD
Certica
RAD-001
Certican
Afinitor
Zortress
Everolimus
CERTICAN(R)
EveroliMus API
EveroliMus(RAD-001)
Everolimus solution
42-O-(2-Hydroxyethyl)-rapamycin
Rapamycin, 42-O-(2-hydroxyethyl)-
23,27-Epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine, rapamycin deriv
(1R,9S,12S,15R,16Z,18R,19R,21R,23S,24Z,26Z,28Z,30S,32S,35R)-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-Methoxycyclohexyl]propan-2-yl]-19,30-diMethoxy-15,17,21,23,29,35-hexaMethyl-11,36-dioxa-4-azatricyclo[30.3.1.0^{4,9}]hexatriaconta-16,2
[Molecular Formula]

C53H83NO14
[MDL Number]

MFCD07785165
[MOL File]

159351-69-6.mol
[Molecular Weight]

958.232
Chemical PropertiesBack Directory
[Appearance]

Off White Solid
[mp ]

NA
[storage temp. ]

−20°C
[Stability:]

Hygroscopic
Hazard InformationBack Directory
[Chemical Properties]

Off White Solid
[Usage]

Everolimus (RAD001) is an mTOR inhibitor of FKBP12 with IC50 of 1.6-2.4 nM
[Usage]

Everolimus is a semi-synthetic macrocyclic lactone prepared from rapamycin by selective alkylation of the 42-hydroxy group with a silyl-protected hydroxyethyl triflate moiety, followed by addition of an ethylhydroxy moiety to provide greater stability and bioavailability. Like all tacrolimus analogues, everolimus binds to receptor protein, FKBP12. The complex then binds to mTOR preventing it from interacting with target proteins. Everolimus is extensively cited in the literature with over 2,000 citations.
[Usage]

Everolimus Macrolide immunosuppressant; Everolimus is a derivative of Rapamycin. Everolimus inhibits cytokine-mediated lymphocyte proliferation.
[Usage]

Macrolide immunosuppressant; derivative of Rapamycin. Inhibits cytokine-mediated lymphocyte proliferation
Safety DataBack Directory
[Hazard Codes ]

T,Xn,F
[Risk Statements ]

48/25-36-20/21/22-11
[Safety Statements ]

45-36/37-26-16
[WGK Germany ]

2
[F ]

10
[HS Code ]

29349990
Questions And AnswerBack Directory
[Overview]

Everolimus is a derivative of Rapamycin(sirolimus), and works similarly to Rapamycin as an mTOR(mammalian target of rapamycin) inhibitor[1-3]. It is currently used as an immunosuppressant to prevent rejection of organ transplants. In a similar fashion to other mTOR inhibitors, Everolimus takes effect solely on the mTORC1 protein and not on the mTORC2 protein[1]. In transplantation medicine, it is marketed under the trade names Zortress(USA) and Certican(Europe)[4]. It has been also used for the treatment of tumors, being marketed as Afinitor(general tumours) and Votubia(tumours as a result of TSC) in oncology[5, 6].
[Indications]

Everolimus is indicated for the treatment of numerous diseases and disorders. It indicated for the treatment of the following cases including both tumors and organ transplantation:
Patients with advance kidney cancer[7];
Postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer(advanced HR+ BC) in combination with exemestane, after failure of treatment with letrozole or anastrozole[8-10];
Adult patients with progressive neuroendocrine tumors of pancreatic origin(PNET) with unresectable, locally advanced or metastatic disease[9, 10];
Adult patients with advanced renal cell carcinoma(RCC) after failure of treatment with sunitinib or sorafenib;
Adult patients with renal angiomyolipoma and tuberous sclerosis complex(TSC), not requiring immediate surgery[11];
Pediatric and adult patients with tuberous sclerosis complex(TSC) for the treatment of subependymal giant cell astrocytoma(SEGA) that requires therapeutic intervention but cannot be curatively resected[12];
Adult and pediatric patients aged 2 years and older with Tuberous Sclerosis Complex(TSC)-associated partial-onset seizures[10];
Preventing the organ rejection during/after renal and liver transplantation[14, 15];
Progressive, well-differentiated non-functional, neuroendocrine tumors[NET] of gastrointestinal(GI) or lung origin with unresectable, locally advanced or metastatic disease[16].
[Mode of action]

The mammalian target of rapamycin(mTOR) pathway is one of the most clinically important molecular signalling networks to emerge over the past decade. It is the protein kinase at the core of this intricate and continually evolving pathway, controls cellular growth and behavior, impacting vital processes from immune reactivity to cancer progression[17, 18]. Everolimus is an mTOR inhibitor that binds with high affinity to the FK506 binding protein-12(FKBP-12), thereby forming a drug complex that inhibits the activation of mTOR[19-20]. This inhibition reduces the activity of effectors downstream, which leads to a blockage in the progression of cells from G1 into S phase, and subsequently inducing cell growth arrest and apoptosis. Everolimus also inhibits the expression of hypoxia-inducible factor, leading to a decrease in the expression of vascular endothelial growth factor[19, 20]. The result of everolimus inhibition of mTOR is a reduction in cell proliferation, angiogenesis, and glucose uptake. Since highly expression of mTOR is an important factor that promoting the cancer, blocking mTOR by Everolimus can effectively treat some kinds of cancer and the organ rejection due to immune response during/after organ transplantation[21, 22].
[Pharmacokinetics]

Oral everolimus is absorbed rapidly, and reaches peak concentration after 1.3–1.8 hours. Steady state is reached within 7 days, and steady-state peak and trough concentrations, and area under the concentration-time curve (AUC), are proportional to dosage. In adults, everolimus pharmacokinetic characteristics do not differ according to age, weight or sex, but bodyweight-adjusted dosages are necessary in children.

[Adverse reactions]

Some serious adverse reactions associated with Everolimus include non-infection pneumonitis, infections, severe hypersensitivity reactions, angioedema with concomitant use of ACE inhibitors, stomatitis, renal failure, impaired wound healing, metabolic disorders and myelosuppression[10]. Various common side effects include Bloating or swelling of the face, arms, hands, lower legs, or fee bloody nose, chest pain or tightness, chills, cough, decreased weight, diarrhea, difficult or labored breathing, difficulty with swallowing, fever, general feeling of discomfort or illness, hoarseness, lower back or side pain, painful or difficult urination, rapid weight gain, sores, ulcers, or white spots on the lips, tongue, or inside the mouth and tingling of the hands or feet[23]. Less common side effects include bleeding gums, bloody urine, blurred vision, burning, crawling, itching, numbness, prickling, or tingling feelings, coughing up blood, extreme tiredness or weakness, fast, pounding, or irregular heartbeat or pulse, increased thirst or urination, irregular breathing, loss of appetite, nausea, nervousness, nosebleeds, prolonged bleeding from cuts, red or black, tarry stools, red or dark brown urine, slow heartbeat, stomach ache, sweating, unusual tiredness or weakness and vomiting[23].
[Warning and precautions]

People who are allergic to Everolimus should be disabled. Since it can increase your risk of serious infections or getting certain cancers, such as lymphoma or skin cancer. The patients should ask their doctor about the specific risk[10, 23].
Patients who have the following conditions should consult for doctor for advice before administration: problem in digesting lactose or galactose(sugar); high cholesterol or triglycerides; liver disease; a heart transplantation; or skin cancer in them or their family members[23].
Since it may harm the unborn baby as well as affect fertility(the capability to have children), women should take effective birth control during administration of Everolimus and for at least eight weeks after stopping drugs. Should consult the doctor for advice if you want to or has become pregnant. It may also affect the fertility of men as well. It is generally not recommended to have breast-feed during the administration of Everolimus for women[10, 23].
[References]

  1. https://www.drugbank.ca/drugs/DB01590
  2. https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm488028.htm
  3. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022334s036lbl.pdf
  4. Junge, G., et al. "EVEROLIMUS, MTORC1 INHIBITION, AND IMPACT ON HEPATOCELLULAR CARCINOMA RECURRENCE AFTER LIVER TRANSPLANTATION-12, 24, AND 36 MONTHS DATA FROM 719 LTX RECIPIENTS." Transplant International 27(2014]: 23-23.
  5. Yao, J. C., et al. "Everolimus for advanced pancreatic neuroendocrine tumors. " New England Journal of Medicine 364.6(2011]: 514-23.
  6. Motzer, Robert J, et al. "Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma." Lancet Oncology 17.7(2016]: 917-927.
  7. Nachtnebel, A. "Everolimus[Afinitor] for advanced/metastatic kidney cancer."[2009].
  8. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm254350.htm
  9. https://www.reuters.com/article/2012/07/20/novartis-afinitor-idUSL2E8IKD8B20120720
  10. https://www.rxlist.com/afinitor-drug.htm#indications_dosage
  11. Matin, Surena F. "Everolimus for the treatment of TSC-associated tumors." Community Oncology 9.12(2012]:361–362.
  12. Cappellano, A. M., et al. "Successful everolimus therapy for SEGA in pediatric patients with tuberous sclerosis complex." Childs Nervous System Chns Official Journal of the International Society for Pediatric Neurosurgery 29.12(2013]:2301-2305.
  13. Bilbao, Itxarone, et al. "Multiple indications for everolimus after liver transplantation in current clinical practice." World Journal of Transplantation 4.2(2014]: 122-132.
  14. Ganschow, Rainer, et al. "The role of everolimus in liver transplantation." Clinical & Experimental Gastroenterology 7.default(2014]:329-343.
  15. Dunn, C, and K. F. Croom. "Everolimus: a review of its use in renal and cardiac transplantation. " Drugs 66.4(2006]:547-570.
  16. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm488028.htm
  17. Geissler, Edward K., H. J. Schlitt, and G. Thomas. "mTOR, Cancer and Transplantation." American Journal of Transplantation 8.11(2010]:2212-2218.
  18. Young, D. A., and C. L. Nickersonnutter. "mTOR--beyond transplantation. " Current Opinion in Pharmacology 5.4(2005]: 418-423.
  19. Anandappa, G., A. Hollingdale, and T. Eisen. "Everolimus – a new approach in the treatment of renal cell carcinoma." Cancer Management & Research 2.1(2010]:61.
  20. Raimondo, L., et al. "Everolimus induces Met inactivation by disrupting the FKBP12/Met complex:" Oncotarget 7.26(2016]:40073-40084.
  21. Sabatini, David M. "mTOR and cancer: insights into a complex relationship." Nature Reviews Cancer 6.9(2006]:729.
  22. Efeyan, Alejo, and D. M. Sabatini. "mTOR and cancer: many loops in one pathway." Current Opinion in Cell Biology 22.2(2010]:169-176.
  23. https://www.drugs.com/mtm/everolimus.html
159351-69-6 suppliers list
Company Name: TianYuan Pharmaceutical CO.,LTD
Tel: +86-755-23284190 13684996853
Fax: +86-755-23284190
Website: www.tianpharm.com
Company Name: Casorganics US Corp
Tel: +17326109938
Fax:
Website: www.chemicalbook.com/ShowSupplierProductsList31338/0.htm
Company Name: ATK CHEMICAL COMPANY LIMITED
Tel: +86 21 5161 9050/ 5187 7795
Fax: +86 21 5161 9052/ 5187 7796
Website: www.atkchemical.com
Company Name: Amadis Chemical Company Limited
Tel: 0086-571-89925085
Fax: 0086-571-89925065
Website: www.amadischem.com
Company Name: Capot Chemical Co.,Ltd.
Tel: +86-571-85586718
Fax: +86-571-85864795
Website: www.capotchem.com
Company Name: Shanghai Arbor Chemical Co., Ltd.
Tel: 021-60451682
Fax: 021-60451683
Website: www.chemicalbook.com/ShowSupplierProductsList31105/0.htm
Company Name: Biochempartner
Tel: 0086-13720134139
Fax:
Website: www.biochempartner.com
Company Name: ENBRIDGE PHARMTECH CO., LTD.
Tel: 13812269233
Fax: 0510-83591909
Website: https://www.chemicalbook.com/ShowSupplierProductsList1053464/0.htm
Company Name: Zhuozhou Wenxi import and Export Co., Ltd
Tel: +8613111626072
Fax: +8613111626072
Website: https://www.chemicalbook.com/ShowSupplierProductsList403210/0.htm
Company Name: CONIER CHEM AND PHARMA LIMITED
Tel: 86-18523575427
Fax:
Website: https://www.chemicalbook.com/ShowSupplierProductsList617604/0.htm
Company Name: Shanghai Yingrui Biopharma Co.,Ltd
Tel: +86-21-33585366
Fax: +86-21-34979012
Website: www.shyrchem.com
Company Name: Chongqing Chemdad Co., Ltd
Tel: +86-13650506873
Fax:
Website: www.chemdad.com
Company Name: Beijing Yibai Biotechnology Co., Ltd
Tel: 0086-182-6772-3597
Fax:
Website: www.chemicalbook.com/ShowSupplierProductsList187389/0.htm
Company Name: NanJing Spring & Autumn Biological Engineering CO., LTD.
Tel: 0086 13770522018
Fax: 0086-25-83337318
Website: www.chemistrynatural.com
Company Name: Xiamen AmoyChem Co., Ltd
Tel: +86 592-605 1114
Fax:
Website: www.amoychem.com
Company Name: Chemwill Asia Co.,Ltd.
Tel: 86-21-51086038
Fax: 86-21-51861608
Website: www.chemwill.com
Company Name: Hubei Jusheng Technology Co.,Ltd.
Tel: 86-18871470254
Fax: 027-59599243
Website: www.hubeijusheng.com
Company Name: Cangzhou Wanyou New Material Technology Co.,Ltd
Tel: 18631714998
Fax:
Website: www.chemicalbook.com/ShowSupplierProductsList1382651/0.htm
Tags:159351-69-6 Related Product Information
141396-28-3 15862-72-3 81854-56-0 53123-88-9 1723-00-8 30727-18-5