Sirolimus (Rapamycin)
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MedKoo CAT#: 100766

CAS#: 53123-88-9

Description: Sirolimus, also known as rapamycin, is a natural macrocyclic lactone produced by the bacterium Streptomyces hygroscopicus, with immunosuppressant properties. In cells, sirolimus binds to the immunophilin FK Binding Protein-12 (FKBP-12) to generate an immunosuppressive complex that binds to and inhibits the activation of the mammalian Target Of Rapamycin (mTOR), a key regulatory kinase. This results in inhibition of T lymphocyte activation and proliferation that occurs in response to antigenic and cytokine (IL-2, IL-4, and IL-15) stimulation and inhibition of antibody production.


Price and Availability

Size
Price

100mg
USD 65
1g
USD 380
10g
USD 2350
Size
Price

200mg
USD 115
2g
USD 650
20g
USD 3950
Size
Price

500mg
USD 210
5g
USD 1250
50g
USD 5950

Sirolimus (Rapamycin), purity > 98%, is in stock. The same day shipping out after order is received. Delivery time: overnight (USA/Canada); 3-5 days (worldwide).


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 100766
Name: Sirolimus (Rapamycin)
CAS#: 53123-88-9
Chemical Formula: C51H79NO13
Exact Mass: 913.55514
Molecular Weight: 914.17
Elemental Analysis: C, 67.01; H, 8.71; N, 1.53; O, 22.75


Synonym: RAPA; RAP; RPM; SLM; AY 22989; AY22989; AY-22989; SILA 9268A; WY090217; WY-090217; WY 090217; C07909; D00753; sirolimus; rapamycin; Rapamune.

IUPAC/Chemical Name: (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34, 34a-hexadecahydro-9,27-dihydroxy-3-[(1R)-2-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethyl]-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido[2,1-c][1,4] oxaazacyclohentriacontine-1,5,11,28,29 (4H,6H,31H)-pentone

InChi Key: QFJCIRLUMZQUOT-PYYJPVDBSA-N

InChi Code: 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

SMILES Code: C[C@@H](C([C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(C[C@@H]([C@H](C)C[C@@H]1CC[C@@H](O)C(OC)C1)OC2=O)=O)=O)C[C@H](C)/C=C/C=C/C=C(C)/[C@@H](OC)C[C@H]3O[C@](C(C(N4[C@H]2CCCC4)=O)=O)(O)[C@H](C)CC3


Technical Data

Appearance:
White to off-white solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Certificate of Analysis:

Safety Data Sheet (MSDS):

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


Additional Information

According to http://en.wikipedia.org/wiki/Sirolimus, Sirolimus (also known as rapamycin) is a chemical that was discovered by Suren Sehgal,[1] as a product of bacteria discovered on Easter Island (the island is also known as Rapa Nui).[2] It was approved by the US Food and Drug Administration in September 1999 and is marketed under the trade name Rapamune by Pfizer (formerly by Wyeth). Sirolimus was originally developed as an antifungal agent. However, this use was abandoned when it was discovered to have potent immunosuppressive and antiproliferative properties. It has since been shown to prolong the life of mice and might also be useful in the treatment of certain cancers.
 
Mechanism of Action
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. Studies in experimental models show that sirolimus prolongs allograft (kidney, heart, skin, islet, small bowel, pancreatico-duodenal, and bone marrow) survival in mice, rats, pigs, and/or primates. Sirolimus reverses acute rejection of heart and kidney allografts in rats and prolongs the graft survival in presensitized rats. In some studies, the immunosuppressive effect of sirolimus lasts up to 6 months after discontinuation of therapy. This tolerization effect is alloantigen-specific. In rodent models of autoimmune disease, sirolimus suppresses immune-mediated events associated with systemic lupus erythematosus, collagen-induced arthritis, autoimmune type I diabetes, autoimmune myocarditis, experimental allergic encephalomyelitis, graft-versus-host disease, and autoimmune uveoretinitis.
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. Studies in experimental models show that sirolimus prolongs allograft (kidney, heart, skin, islet, small bowel, pancreatico-duodenal, and bone marrow) survival in mice, rats, pigs, and/or primates. Sirolimus reverses acute rejection of heart and kidney allografts in rats and prolongs the graft survival in presensitized rats. In some studies, the immunosuppressive effect of sirolimus lasts up to 6 months after discontinuation of therapy. This tolerization effect is alloantigen-specific. In rodent models of autoimmune disease, sirolimus suppresses immune-mediated events associated with systemic lupus erythematosus, collagen-induced arthritis, autoimmune type I diabetes, autoimmune myocarditis, experimental allergic encephalomyelitis, graft-versus-host disease, and autoimmune uveoretinitis.


References

1: Knoll GA, Kokolo MB, Mallick R, Beck A, Buenaventura CD, Ducharme R, Barsoum R, Bernasconi C, Blydt-Hansen TD, Ekberg H, Felipe CR, Firth J, Gallon L, Gelens M, Glotz D, Gossmann J, Guba M, Morsy AA, Salgo R, Scheuermann EH, Tedesco-Silva H, Vitko S, Watson C, Fergusson DA. Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data. BMJ. 2014 Nov 24;349:g6679. doi: 10.1136/bmj.g6679. Review. PubMed PMID: 25422259; PubMed Central PMCID: PMC4241732.

2: Peng ZF, Yang L, Wang TT, Han P, Liu ZH, Wei Q. Efficacy and safety of sirolimus for renal angiomyolipoma in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis: a systematic review. J Urol. 2014 Nov;192(5):1424-30. doi: 10.1016/j.juro.2014.04.096. Epub 2014 May 9. Review. PubMed PMID: 24813310.

3: Woudstra P, de Winter RJ, Beijk MA. Next-generation DES: the COMBO dual therapy stent with Genous endothelial progenitor capturing technology and an abluminal sirolimus matrix. Expert Rev Med Devices. 2014 Mar;11(2):121-35. doi: 10.1586/17434440.2014.882046. Epub 2014 Feb 3. Review. PubMed PMID: 24484431.

4: Choe H, Aldoss I, Chaudhary P, Donovan J, Petrovic L, Pullarkat V. Nodular regenerative hyperplasia causing portal hypertension in a patient with chronic graft versus host disease: response to sirolimus. Acta Haematol. 2014;132(1):49-52. doi: 10.1159/000356736. Epub 2014 Jan 15. Review. PubMed PMID: 24434665.

5: Qiao Y, Bian Y, Yan X, Liu Z, Chen Y. Efficacy and safety of sirolimus-eluting stents versus bare-metal stents in coronary artery disease patients with diabetes: a meta-analysis. Cardiovasc J Afr. 2013 Aug;24(7):274-9. doi: 10.5830/CVJA-2013-062. Review. PubMed PMID: 24217305; PubMed Central PMCID: PMC3807685.

6: Dasari TW, Patel B, Saucedo JF. Systematic review of effectiveness of oral sirolimus after bare-metal stenting of coronary arteries for prevention of in-stent restenosis. Am J Cardiol. 2013 Nov 1;112(9):1322-7. doi: 10.1016/j.amjcard.2013.05.074. Epub 2013 Aug 6. Review. PubMed PMID: 23932188.

7: Lemos PA, Bienert I. The Supralimus sirolimus-eluting stent. Expert Rev Med Devices. 2013 May;10(3):295-300. doi: 10.1586/erd.12.91. Epub 2013 Apr 18. Review. PubMed PMID: 23597097.

8: Tartarin P, Froment P. [mTORC1 and sirolimus: a link with fertility]. Med Sci (Paris). 2013 Feb;29(2):200-5. doi: 10.1051/medsci/2013292019. Epub 2013 Feb 28. Review. French. PubMed PMID: 23452608.

9: Park KW, Kang SH, Velders MA, Shin DH, Hahn S, Lim WH, Yang HM, Lee HY, Van Boven AJ, Hofma SH, Kang HJ, Koo BK, Oh BH, Park YB, Kandzari DE, Kim HS. Safety and efficacy of everolimus- versus sirolimus-eluting stents: a systematic review and meta-analysis of 11 randomized trials. Am Heart J. 2013 Feb;165(2):241-50.e4. doi: 10.1016/j.ahj.2012.08.007. Epub 2012 Dec 27. Review. PubMed PMID: 23351828.

10: Halleck F, Duerr M, Waiser J, Huber L, Matz M, Brakemeier S, Liefeldt L, Neumayer HH, Budde K. An evaluation of sirolimus in renal transplantation. Expert Opin Drug Metab Toxicol. 2012 Oct;8(10):1337-56. doi: 10.1517/17425255.2012.719874. Epub 2012 Aug 28. Review. PubMed PMID: 22928953.