Back سيروليموس Arabic سیرولیموس AZB Sirolimus Czech Sirolimus German Sirólimus Spanish Sirolimus Basque سیرولیموس Persian Sirolimuusi Finnish Sirolimus French רפמיצין HE
 | |
 | |
| Clinical data | |
|---|---|
| Trade names | Rapamune, Fyarro, Hyftor |
| Other names | Rapamycin, ABI-009 |
| License data | |
| Pregnancy category |
|
| Routes of administration | By mouth, intravenous, topical |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | 14% (oral solution), lower with high-fat meals; 18% (tablet), higher with high-fat meals[7] |
| Protein binding | 92% |
| Metabolism | Liver |
| Elimination half-life | 57–63 hours[8] |
| Excretion | Mostly fecal |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| ChEMBL | |
| PDB ligand | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.107.147 |
| Chemical and physical data | |
| Formula | C51H79NO13 |
| Molar mass | 914.187 g·mol−1 |
| 3D model (JSmol) | |
| Solubility in water | 0.0026 [9] |
| |
| |
| (verify) | |
Sirolimus, also known as rapamycin and sold under the brand name Rapamune among others, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection, treat a rare lung disease called lymphangioleiomyomatosis, and treat perivascular epithelioid cell tumour (PEComa).[2][3][10][11] It has immunosuppressant functions in humans and is especially useful in preventing the rejection of kidney transplants. It is a mechanistic target of rapamycin (mTOR) kinase inhibitor[3] that reduces the sensitivity of T cells and B cells to interleukin-2 (IL-2), inhibiting their activity.[12]
This compound also has a use in cardiovascular drug-eluting stent technologies to inhibit restenosis.
It is produced by the bacterium Streptomyces hygroscopicus and was isolated for the first time in 1972, from samples of Streptomyces hygroscopicus found on Easter Island.[13][14][15] The compound was originally named rapamycin after the native name of the island, Rapa Nui.[10] Sirolimus was initially developed as an antifungal agent. However, this use was abandoned when it was discovered to have potent immunosuppressive and antiproliferative properties due to its ability to inhibit mTOR. It was approved by the U.S. Food and Drug Administration (FDA) in September 1999.[16] Hyftor was approved for treatment of facial angiofibroma in the European Union in May 2023.[6]
- ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
- ^ a b "Rapamune- sirolimus solution Rapamune- sirolimus tablet, sugar coated". DailyMed. Archived from the original on 27 November 2021. Retrieved 26 November 2021.
- ^ a b c "Fyarro- sirolimus injection, powder, lyophilized, for suspension". DailyMed. Archived from the original on 19 December 2021. Retrieved 19 December 2021.
- ^ "Hyftor- sirolimus gel". DailyMed. 28 January 2021. Archived from the original on 24 March 2022. Retrieved 23 March 2022.
- ^ "Rapamune EPAR". European Medicines Agency. 17 September 2018. Archived from the original on 13 August 2021. Retrieved 26 November 2021.
- ^ a b "Hyftor EPAR". European Medicines Agency (EMA). 9 June 2023. Retrieved 12 June 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
- ^ Buck ML (2006). "Immunosuppression With Sirolimus After Solid Organ Transplantation in Children". Pediatric Pharmacotherapy. 12 (2). Archived from the original on 18 April 2020. Retrieved 4 April 2022.
- ^ Cite error: The named reference
Pubchem Rapamycinwas invoked but never defined (see the help page). - ^ Simamora P, Alvarez JM, Yalkowsky SH (February 2001). "Solubilization of rapamycin". International Journal of Pharmaceutics. 213 (1–2): 25–29. doi:10.1016/s0378-5173(00)00617-7. PMID 11165091.
- ^ a b Vézina C, Kudelski A, Sehgal SN (October 1975). "Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle". The Journal of Antibiotics. 28 (10): 721–726. doi:10.7164/antibiotics.28.721. PMID 1102508.
- ^ Cite error: The named reference
Cypherwas invoked but never defined (see the help page). - ^ Cite error: The named reference
Mukherjee_2009was invoked but never defined (see the help page). - ^ Qari S, Walters P, Lechtenberg S (21 May 2021). "The Dirty Drug and the Ice Cream Tub". Radiolab. Archived from the original on 25 July 2021. Retrieved 25 July 2021.
- ^ Seto B (November 2012). "Rapamycin and mTOR: a serendipitous discovery and implications for breast cancer". Clinical and Translational Medicine. 1 (1): 29. doi:10.1186/2001-1326-1-29. PMC 3561035. PMID 23369283.
- ^ Pritchard DI (May 2005). "Sourcing a chemical succession for cyclosporin from parasites and human pathogens". Drug Discovery Today. 10 (10): 688–691. doi:10.1016/S1359-6446(05)03395-7. PMID 15896681.
- ^ "Drug Approval Package: Rapamune (Sirolimus) NDA# 021083". U.S. Food and Drug Administration (FDA). Archived from the original on 1 February 2022. Retrieved 1 February 2022.