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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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
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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
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.
Drugs, 77 (18): 1935-1966. [PMID:29143192]
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.
Biochem J, 451 (2): 313-28. [PMID:23398362]
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]