Tìm theo
Sirolimus
Các tên gọi khác (2) :
  • (-)-Rapamycin
  • Rapamycin
Thuốc trị ký sinh trùng, chống nhiễm khuẩn
Thuốc Gốc
Small Molecule
CAS: 53123-88-9
ATC: L04AA10
ĐG : Cardinal Health , http://www.cardinal.com
CTHH: C51H79NO13
PTK: 914.1719
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]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C51H79NO13
Phân tử khối
914.1719
Monoisotopic mass
913.555141619
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
InChIKey=QFJCIRLUMZQUOT-KLHQEZAJSA-N
IUPAC Name
(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
Traditional IUPAC Name
(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
SMILES
[H][C@@]1(C[C@H](C)[C@]2([H])CC(=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](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](O)[C@@H](C1)OC
Độ hòa tan
1.73e-03 g/l
logP
4.3
logS
-5.7
pKa (strongest acidic)
9.96
pKa (Strongest Basic)
-3
PSA
195.43 Å2
Refractivity
250.66 m3·mol-1
Polarizability
100.46 Å3
Rotatable Bond Count
6
H Bond Acceptor Count
12
H Bond Donor Count
3
Physiological Charge
0
Number of Rings
4
Bioavailability
0
MDDR-Like Rule
true
Dược Lực Học : 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.
Cơ Chế Tác Dụng : 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] 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.
Dược Động Học :

▧ Protein binding :
92%
▧ Half Life :
57-63 hours
Chỉ Định : For the prophylaxis of organ rejection in patients receiving renal transplants.
Tương Tác Thuốc :
  • 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
  • Rifampicin 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.
Liều Lượng & Cách Dùng : Solution - Oral
Tablet - Oral
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Rapamune 0.5 mg tablet
    Giá bán buôn : USD >5.86
    Đơn vị tính : tablet
  • Biệt dược thương mại : Rapamune 1 mg tablet
    Giá bán buôn : USD >11.95
    Đơn vị tính : tablet
  • Biệt dược thương mại : Rapamune 1 mg/ml Solution
    Giá bán buôn : USD >12.19
    Đơn vị tính : ml
  • Biệt dược thương mại : Rapamune 2 mg tablet
    Giá bán buôn : USD >20.59
    Đơn vị tính : tablet
Nhà Sản Xuất
  • Công ty : Wyeth Pharma
    Sản phẩm biệt dược : Rapamune
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00877
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07909
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00753
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50240955
PharmGKB
http://www.pharmgkb.org/drug/PA451365
Wikipedia
http://en.wikipedia.org/wiki/Sirolimus
RxList
http://www.rxlist.com/cgi/generic2/sirolimus.htm
Drugs.com
http://www.drugs.com/cdi/sirolimus.html
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