Rapamycin
[CAS# 53123-88-9]

Identification

• Classification: API >> Immune function drug >> Immunosuppressive drug
• Name: Rapamycin
• Synonyms: 23,27-Epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine; Sirolimus; (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-hydroxy-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: C₅₁H₇₉NO₁₃
• Molecular Weight: 914.18
• CAS Registry Number: 53123-88-9
• EC Number: 610-965-5
• 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)O)C)/C)O)OC)C)C)/C)OC

Properties

• Density: 1.2±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.551, Calc.^*
• Boiling Point: 973.0±75.0 °C (760 mmHg), Calc.^*
• Flash Point: 542.3±37.1 °C, Calc.^*

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

Safety Data

• Hazard Symbols: GHS08 Danger
• Risk Statements: H341-H351-H361-H372
• Safety Statements: P203-P260-P264-P270-P280-P318-P319-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Reproductive toxicity	Repr.	2	H361
Carcinogenicity	Carc.	2	H351
Germ cell mutagenicity	Muta.	2	H341
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Reproductive toxicity	Repr.	1B	H360
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Specific target organ toxicity - single exposure	STOT SE	2	H371
Acute toxicity	Acute Tox.	4	H302
Reproductive toxicity	Repr.	2	H361fd
Specific target organ toxicity - repeated exposure	STOT RE	2	H373

Discovery and Applications

Rapamycin, also known as sirolimus, was discovered in the 1970s by researchers at the Canadian-based Ayerst Laboratories (now Pfizer Inc.) from soil samples collected on Easter Island, also known as Rapa Nui. Initially isolated as a byproduct of Streptomyces hygroscopicus fermentation, rapamycin was found to possess potent immunosuppressive properties. Its name "rapamycin" is derived from "Rapa Nui" and "mycin," indicating its origin and antibiotic nature, respectively. The discovery of rapamycin represented a significant breakthrough in immunology and paved the way for its diverse medical applications.

Rapamycin is widely used in organ transplantation to prevent graft rejection. As an immunosuppressant, it inhibits the activation and proliferation of T-lymphocytes, a key component of the immune response against foreign tissues. When used in combination with other immunosuppressive agents such as cyclosporine and corticosteroids, rapamycin helps prevent acute rejection episodes and prolongs graft survival in kidney, liver, heart, and lung transplant recipients. Rapamycin has shown 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 the mammalian target of rapamycin (mTOR) pathway, rapamycin suppresses cell growth and proliferation, slowing the progression of LAM and improving lung function in affected individuals. Rapamycin and its analogs, collectively known as mTOR inhibitors, have emerged as promising agents in cancer therapy. By targeting the mTOR signaling pathway, which regulates cell growth, proliferation, and survival, rapamycin inhibits tumor growth and angiogenesis in various malignancies, including renal cell carcinoma, breast cancer, and neuroendocrine tumors. Rapamycin has demonstrated efficacy in the treatment of rare genetic disorders such as tuberous sclerosis complex (TSC) and focal segmental glomerulosclerosis (FSGS). In TSC, rapamycin inhibits the overactivation of the mTOR pathway, reducing the growth of benign tumors in various organs. In FSGS, rapamycin may help preserve kidney function by reducing proteinuria and delaying disease progression.

References

2021. Genetic pathogenesis of the epileptogenic lesions in Tuberous Sclerosis Complex: Therapeutic targeting of the mTOR pathway. Epilepsy & Behavior, 131(Pt B).
DOI: 10.1016/j.yebeh.2020.107713

2021. The effects of mTOR or Vps34-mediated autophagy on methylmercury-induced neuronal apoptosis in rat cerebral cortex. Food and Chemical Toxicology, 155.
DOI: 10.1016/j.fct.2021.112386

2021. AMPK Inhibits mTOR-Driven Keratinocyte Proliferation after Skin Damage and Stress. The Journal of Investigative Dermatology, 141(9).
DOI: 10.1016/j.jid.2020.12.036