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药品详细

Sirolimus(西罗莫司)

化学结构式图
中文名
西罗莫司
英文名
Sirolimus
分子式
C51H79NO13
化学名
(1R,9S,12S,15R,18R,19R,21R,23S,30S,32S,35R)-1,18-dihydroxy-12-[(2S)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.0^{4,9}]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone
分子量
Average: 914.1719
Monoisotopic: 913.555141619
CAS号
53123-88-9
ATC分类
L04A 未知
药物类型
small molecule
阶段
approved
商品名
Rapamune;Rapamycin;
同义名
Antibiotic AY 22989;rapamycin;sirolimus;
基本介绍

A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to immunophilins. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. [PubChem]

生产厂家
  • Wyeth pharmaceuticals inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Pritchard DI: Sourcing a chemical succession for cyclosporin from parasites and human pathogens. Drug Discov Today. 2005 May 15;10(10):688-91. Pubmed
  2. Shuchman M: Trading restenosis for thrombosis? New questions about drug-eluting stents. N Engl J Med. 2006 Nov 9;355(19):1949-52. Pubmed
  3. Sun SY, Rosenberg LM, Wang X, Zhou Z, Yue P, Fu H, Khuri FR: Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition. Cancer Res. 2005 Aug 15;65(16):7052-8. Pubmed
  4. Chan S: Targeting the mammalian target of rapamycin (mTOR): a new approach to treating cancer. Br J Cancer. 2004 Oct 18;91(8):1420-4. Pubmed
  5. Graziani EI: Recent advances in the chemistry, biosynthesis and pharmacology of rapamycin analogs. Nat Prod Rep. 2009 May;26(5):602-9. Epub 2009 Mar 5. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes Not Available
Substructures Not Available
适应症
;IMMUNOSUPPRESSIVE 免疫抑制;
药理
Indication For the prophylaxis of organ rejection in patients receiving renal transplants.
Pharmacodynamics Sirolimus, a macrocyclic lactone produced by Streptomyces hygroscopicus, is an immunosuppressive agent indicated for the prophylaxis of organ rejection in patients receiving renal transplants. It is recommended that sirolimus be used in a regimen with cyclosporine and corticosteroids.
Mechanism of action Sirolimus inhibits T lymphocyte activation and proliferation that occurs in response to antigenic and cytokine (Interleukin IL-2, IL-4, and IL-15) stimulation by a mechanism that is distinct from that of other immunosuppressants. Sirolimus also inhibits antibody production. In cells, sirolimus binds to the immunophilin, FK Binding Protein-12 (FKBP-12), to generate an immunosuppressive complex. The sirolimus:FKBP-12 complex has no effect on calcineurin activity. This complex binds to and inhibits the activation of the mammalian Target Of Rapamycin (mTOR), a key regulatory kinase. This inhibition suppresses cytokine-driven T-cell proliferation, inhibiting the progression from the G1 to the S phase of the cell cycle.
Absorption Not Available
Volume of distribution Not Available
Protein binding 92%
Metabolism
Not Available

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Sirolimus
41-O-demethylrapamycin Details
Route of elimination Not Available
Half life 57-63 hours
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
logP 4.3 Not Available
Predicted Properties
Property Value Source
water solubility 1.73e-03 g/l ALOGPS
logP 4.85 ALOGPS
logP 7.45 ChemAxon
logS -5.7 ALOGPS
pKa (strongest acidic) 9.96 ChemAxon
pKa (strongest basic) -3 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 12 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 195.43 ChemAxon
rotatable bond count 6 ChemAxon
refractivity 250.66 ChemAxon
polarizability 100.46 ChemAxon
药物相互作用
Drug Interaction
Atazanavir Increases the effect and toxicity of immunosuppressant
Boceprevir Boceprevir increases levels of sirolimus by affecting CYP3A4 metabolism. Concomitant therapy requires close monitoring.
Clarithromycin The macrolide, clarithromycin, may increase the serum concentration of sirolimus.
Cyclosporine Increases the effect and toxicity of sirolimus
Diltiazem Increases the effect and toxicity of sirolimus
Dronedarone Sirolimus is a CYP3A substrate with a narrow therapeutic index thus concomitant therapy with dronedarone will increase plasma levels of sirolimus. Monitor plasma concentrations and adjust dose accordingly.
Erythromycin The macrolide, erythromycin, may increase the serum concentration of sirolimus.
Fosphenytoin The hydantoin decreases sirolimus levels
Itraconazole Itraconazole may increase the effect and toxicity of sirolimus.
Ketoconazole Ketoconazole may increase the effect and toxicity of sirolimus.
Phenytoin The hydantoin decreases sirolimus levels
Rifabutin The rifamycin decreases the effect of sirolimus
Rifampin The rifamycin decreases the effect of sirolimus
Rilonacept results in increased immunosuppressive effects; increases the risk of infection.
Tacrolimus Sirolimus may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Sirolimus therapy is initiated, discontinued or altered.
Telithromycin Telithromycin may reduce clearance of Sirolimus. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Sirolimus if Telithromycin is initiated, discontinued or dose changed.
Tipranavir Tipranavir may affect the efficacy/toxicity of Sirolimus.
Trandolapril Increased risk of angioedema. Monitor for signs and symptoms of facial and systemic edema and/or erythema.
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Voriconazole Voriconazole may increase the serum concentration of sirolimus likely by inhibition of CYP3A4-mediated metabolism or p-glyprotein transport of sirolimus. Consider alternate therapy or reduce the dose of sirolimus and monitor serum levels during concomitant therapy.
食物相互作用
Not Available

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