sirolimus   Click here for help

GtoPdb Ligand ID: 6031

Synonyms: AY-22989 | Fyarro® (sirolimus albumin-bound particles) | 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. Sirolimus is classified as a Type IV allosteric kinase inhibitor [10].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

IUPHAR Pharmacology Education Project (PEP) logo

View more information in the IUPHAR Pharmacology Education Project: sirolimus

sirolimus is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Click here for structure editor
Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011)
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.
Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]
2. Chen J, Zheng XF, Brown EJ, Schreiber SL. (1995)
Identification of an 11-kDa FKBP12-rapamycin-binding domain within the 289-kDa FKBP12-rapamycin-associated protein and characterization of a critical serine residue.
Proc Natl Acad Sci USA, 92 (11): 4947-51. [PMID:7539137]
3. Chiu MI, Katz H, Berlin V. (1994)
RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin complex.
Proc Natl Acad Sci USA, 91 (26): 12574-8. [PMID:7809080]
4. Dyall J, Gross R, Kindrachuk J, Johnson RF, Olinger Jr GG, Hensley LE, Frieman MB, Jahrling PB. (2017)
Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome: Current Therapeutic Options and Potential Targets for Novel Therapies.
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5. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013)
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.
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6. Hamilton GS, Steiner JP. (1998)
Immunophilins: beyond immunosuppression.
J Med Chem, 41 (26): 5119-43. [PMID:9857082]
7. Kelly PA, Gruber SA, Behbod F, Kahan BD. (1997)
Sirolimus, a new, potent immunosuppressive agent.
Pharmacotherapy, 17 (6): 1148-56. [PMID:9399599]
8. Kindrachuk J, Ork B, Hart BJ, Mazur S, Holbrook MR, Frieman MB, Traynor D, Johnson RF, Dyall J, Kuhn JH et al.. (2015)
Antiviral potential of ERK/MAPK and PI3K/AKT/mTOR signaling modulation for Middle East respiratory syndrome coronavirus infection as identified by temporal kinome analysis.
Antimicrob Agents Chemother, 59 (2): 1088-99. [PMID:25487801]
9. Kopparthy P, Murphy M. (2021)
Rapid and Durable Response With Nab-Sirolimus After Everolimus Failure in a Patient With Perivascular Epithelioid Cell Tumors (PEComas) of the Uterus.
Cureus, 13 (5): e14951. DOI: 10.7759/cureus.14951 [PMID:34123648]
10. Li J, Kim SG, Blenis J. (2014)
Rapamycin: one drug, many effects.
Cell Metab, 19 (3): 373-9. [PMID:24508508]
11. McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM et al.. (2011)
Efficacy and safety of sirolimus in lymphangioleiomyomatosis.
N Engl J Med, 364 (17): 1595-606. [PMID:21410393]
12. Vasquez EM. (2000)
Sirolimus: a new agent for prevention of renal allograft rejection.
Am J Health Syst Pharm, 57 (5): 437-48; quiz 449-51. [PMID:10711524]
13. Vilella-Bach M, Nuzzi P, Fang Y, Chen J. (1999)
The FKBP12-rapamycin-binding domain is required for FKBP12-rapamycin-associated protein kinase activity and G1 progression.
J Biol Chem, 274 (7): 4266-72. [PMID:9933627]
14. Wagner AJ, Ravi V, Riedel RF, Ganjoo K, Van Tine BA, Chugh R, Cranmer L, Gordon EM, Hornick JL, Du H et al.. (2021)
nab-Sirolimus for Patients With Malignant Perivascular Epithelioid Cell Tumors.
J Clin Oncol, 39 (33): 3660-3670. [PMID:34637337]