sirolimus   Click here for help

GtoPdb Ligand ID: 6031

Synonyms: AY-22989 | Rapamune® | rapamycin | WY-090217
Approved drug PDB Ligand Immunopharmacology Ligand
sirolimus is an approved drug (FDA (1999), EMA (2001))
Compound class: Synthetic organic
Comment: Sirolimus is a macrolide produced by the bacteria Streptomyces hygroscopicus. It has potent immunosuppressive and antiproliferative properties.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 14
Hydrogen bond donors 3
Rotatable bonds 6
Topological polar surface area 195.43
Molecular weight 913.56
XLogP 4.32
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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Canonical SMILES COC1CC(CCC1O)CC(C1OC(=O)C2CCCCN2C(=O)C(=O)C2(O)OC(CCC2C)CC(OC)C(=CC=CC=CC(CC(C(=O)C(C(C(=CC(C(=O)C1)C)C)O)OC)C)C)C)C
Isomeric SMILES CO[C@@H]1C[C@@H](CC[C@H]1O)C[C@H]([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H](CC[C@H]2C)C[C@H](OC)/C(=C/C=C/C=C/[C@H](C[C@H](C(=O)[C@@H]([C@@H](/C(=C/[C@H](C(=O)C1)C)/C)O)OC)C)C)/C)C
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
InChI Key QFJCIRLUMZQUOT-HPLJOQBZSA-N
No information available.
Summary of Clinical Use Click here for help
Sirolimus is used for prophylaxis of renal transplant rejection [7,10], and may be used in combination with cyclosporin A. In June 2015 the US FDA approved sirolimus for the treatment of lymphangioleiomyomatosis, a rare proliferative but benign lung disease [9].
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Sirolimus binds to the FK506 binding protein 12 (FKBP12), creating a complex which inhibits mammalian target of rapamycin (mTOR). The FKBP12-sirolimus complex is reported to bind to a site distinct from the kinase domain of mTOR and acts as a negative allosteric modulator of mTOR activity [2-3]. This action reduces mTOR-induced proliferation of activated T-cells, the cells which would normally be involved in the immunological attack on transplanted tissue [7,11].
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