Everolimus
[CAS# 159351-69-6]

Identification

• Classification: API >> Immune function drug >> Immunosuppressive drug
• Name: Everolimus
• Synonyms: (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,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[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone
• Molecular Formula: C₅₃H₈₃NO₁₄
• Molecular Weight: 958.22
• CAS Registry Number: 159351-69-6
• EC Number: 621-003-9
• SMILES: C[C@@H]1CC[C@H]2C[C@@H](/C(=C/C=C/C=C/[C@H](C[C@H](C(=O)[C@@H]([C@@H](/C(=C/[C@H](C(=O)C[C@H](OC(=O)[C@@H]3CCCCN3C(=O)C(=O)[C@@]1(O2)O)[C@H](C)C[C@@H]4CC[C@H]([C@@H](C4)OC)OCCO)C)/C)O)OC)C)C)/C)OC

Properties

• Density: 1.2±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.548, Calc.^*
• Boiling Point: 998.7±75.0 °C (760 mmHg), Calc.^*
• Flash Point: 557.8±37.1 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS08 Danger
• Risk Statements: H372-H412
• Safety Statements: P260-P264-P270-P273-P319-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412
Carcinogenicity	Carc.	2	H351
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Reproductive toxicity	Repr.	1B	H360Fd
Reproductive toxicity	Lact.	-	H362
Reproductive toxicity	Repr.	2	H361
Chronic hazardous to the aquatic environment	Aquatic Chronic	4	H413
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411

Discovery and Applications

Everolimus, a derivative of rapamycin, was developed in the late 1990s by researchers at Novartis Pharmaceuticals. It was synthesized through modifications to the rapamycin molecule to enhance its pharmacokinetic properties and optimize its therapeutic efficacy. Everolimus belongs to the class of drugs known as mammalian target of rapamycin (mTOR) inhibitors, which selectively inhibit the mTOR pathway involved in cell growth, proliferation, and survival. The discovery of everolimus represented a significant advancement in targeted cancer therapy.

Everolimus is approved for the treatment of various advanced solid tumors, including renal cell carcinoma (RCC), pancreatic neuroendocrine tumors (pNET), and hormone receptor-positive, HER2-negative breast cancer. As an mTOR inhibitor, everolimus blocks aberrant signaling pathways implicated in tumor growth and angiogenesis, slowing disease progression and extending progression-free survival in patients with these malignancies. Everolimus is used in combination with other immunosuppressive agents for the prevention of organ rejection in transplant recipients. By inhibiting T-cell activation and proliferation, everolimus helps maintain graft function and reduce the risk of acute rejection episodes in kidney, liver, heart, and lung transplant recipients. Everolimus is indicated for the treatment of tuberous sclerosis complex (TSC), a rare genetic disorder characterized by the growth of benign tumors in multiple organs, including the brain, kidneys, and skin. By inhibiting the mTOR pathway, everolimus reduces tumor growth and alleviates symptoms associated with TSC, such as seizures, renal angiomyolipomas, and skin lesions. Everolimus has demonstrated efficacy in the treatment of lymphangioleiomyomatosis (LAM), a rare progressive lung disease characterized by abnormal smooth muscle cell proliferation in the lungs and lymphatic vessels. By inhibiting mTOR signaling, everolimus suppresses cell proliferation and stabilizes lung function in patients with LAM, reducing the risk of disease progression and improving quality of life.

References

2005. Adjusted indirect comparison of intracoronary drug-eluting stents: evidence from a metaanalysis of randomized bare-metal-stent-controlled trials. International Journal of Cardiology, 100(1), 119-123.
DOI: https://pubmed.ncbi.nlm.nih.gov/1582026

2009. Oral mTOR Inhibitor Everolimus in Patients With Gemcitabine-Refractory Metastatic Pancreatic Cancer. Journal of clinical oncology, 27/global2), 135-798.
DOI: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645085

2010. Updated recommendations from the Spanish Oncology Genitourinary Group on the treatment of advanced renal cell carcinoma. Cancer, 29(3), 2020-498.
DOI: https://pubmed.ncbi.nlm.nih.gov/206/10