Sirolimus

Sirolimus
Clinical data


Trade names	Rapamune
License data	EU EMA: Rapamune US FDA: Sirolimus
Pregnancy category	AU: C US: C (Risk not ruled out)
Routes of administration	Oral
ATC code	L04AA10 (WHO) S01XA23 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Bioavailability	14% (oral solution), lower with high-fat meals; 18% (tablet), higher with high-fat meals
Protein binding	92%
Metabolism	Hepatic
Biological half-life	57–63 hours
Excretion	Mostly faecal
Identifiers
IUPAC name (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]-2-propanyl}- 19,30-dimethoxy-15,17,21,23,29,35-hexamethyl- 11,36-dioxa-4-azatricyclo[30.3.1.0~4,9~]hexatria conta-16,24,26,28-tetraene-2,3,10,14,20-pentone
Synonyms	Rapamycin
CAS Number	53123-88-9^Y
PubChem CID	5284616
DrugBank	DB00877^Y
ChemSpider	10482078^Y
UNII	W36ZG6FT64
KEGG	D00753^Y
ChEBI	CHEBI:9168^Y
ChEMBL	CHEMBL413^Y
PDB ligand	RAP (PDBe, RCSB PDB)
ECHA InfoCard	100.107.147
Chemical and physical data
Formula	C₅₁H₇₉NO₁₃
Molar mass	914.172 g/mol
3D model (Jmol)	Interactive image
Solubility in water	0.0026 mg/mL (20 °C)
SMILES O[C@@H]1CC[C@H](C[C@H]1OC)C[C@@H](C)[C@@H]4CC(=O)[C@H](C)/C=C(\C)[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\C=C\C=C\C=C(/C)[C@@H](OC)C[C@@H]2CC[C@@H](C)[C@@](O)(O2)C(=O)C(=O)N3CCCC[C@H]3C(=O)O4
InChI InChI=1S/C51H79NO13/c1-30-16-12-11-13-17-31(2)42(61-8)28-38-21-19-36(7)51(60,65-38)48(57)49(58)52-23-15-14-18-39(52)50(59)64-43(33(4)26-37-20-22-40(53)44(27-37)62-9)29-41(54)32(3)25-35(6)46(56)47(63-10)45(55)34(5)24-30/h11-13,16-17,25,30,32-34,36-40,42-44,46-47,53,56,60H,14-15,18-24,26-29H2,1-10H3/b13-11+,16-12+,31-17+,35-25+/t30-,32-,33-,34-,36-,37+,38+,39+,40-,42+,43+,44-,46-,47+,51-/m1/s1^Y Key:QFJCIRLUMZQUOT-HPLJOQBZSA-N^Y

Sirolimus, also known as rapamycin, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection and to treat a rare lung disease called lymphangioleiomyomatosis. It has immunosuppressant functions in humans and is especially useful in preventing the rejection of kidney transplants. It inhibits activation of T cells and B cells by reducing the production of interleukin-2 (IL-2).

It is produced by the bacterium Streptomyces hygroscopicus and was isolated for the first time in 1972 by Suren Sehgal and colleagues from samples of Streptomyces hygroscopicus found on Easter Island. The compound was originally named rapamycin after the native name of the island, Rapa Nui. 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 US Food and Drug Administration in September 1999 and is marketed under the trade name Rapamune by Pfizer (formerly by Wyeth).

Sirolimus is indicated for the prevention of organ transplant rejection and for the treatment of lymphangioleiomyomatosis (LAM).

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