2963 T3D2921 Sirolimus 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] 53123-88-9 46835353 C51H79NO13 913.555140 White powder. 183-185°C 1.73e-03 g/L Oral 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. Half Life: 57-63 hours LD50: >800 mg/kg (oral, rat) (L1874) LD50: >800 mg/kg (oral, mice) (L1874) No indication of carcinogenicity to humans (not listed by IARC). Used to prevent rejection in organ transplantation; it is especially useful in kidney transplants. [Wikipedia] Increased susceptibility to infection, lymphoma, and malignancy; bronchial anastomotic dehiscence in lung transplant patients; decline in renal function in long-term combination of cyclosporine with Rapamune; proteinuria. (L1874) The most common ( ≥ 30%) adverse reactions observed with Rapamune in clinical studies are: peripheral edema, hypertriglyceridemia, hypertension, hypercholesterolemia, creatinine increased, constipation, abdominal pain, diarrhea, headache, fever, urinary tract infection, anemia, nausea, arthralgia, pain, and thrombocytopenia. (L1874) General supportive measures should be followed in all cases of overdose. Based on the low aqueous solubility and high erythrocyte and plasma protein binding of sirolimus, it is anticipated that sirolimus is not dialyzable to any significant extent. (L1712) 2009-07-21T20:27:53Z 2014-12-24T20:25:53Z Sirolimus C07909 9168 Sirolimus DB00877 RAP true COC1CC(CC(C)C2CC(=O)C(C)C=C(C)C(O)C(OC)C(=O)C(C)CC(C)C=CC=CC=C(C)C(CC3CCC(C)C(O)(O3)C(=O)C(=O)N3CCCCC3C(=O)O2)OC)CCC1O C51H79NO13 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+ InChIKey=QFJCIRLUMZQUOT-LYULEKIKSA-N 914.1719 913.555141619 Exogenous Solid 4.3 HMDB15015 CHEMBL413 21864757 <p>Madhup K. Dhaon, Chi-nung Hsiao, Subhash R. Patel, Peter J. Bonk, Sanjay R. Chemburkar, Yong Y. Chen, &#8220;One pot synthesis of tetrazole derivatives of sirolimus.&#8221; U.S. Patent US20080167335, issued July 10, 2008.</p>