Sirolimus

Sirolimus
(IUPAC) ime
	(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-heksadekahidro-9,27-dihidroksi-3-; [(1R)-2-[(1S,3R,4R)-4-hidroksi-3-metoksicikloheksil]-; 1-metiletil]-10,21-dimetoksi-6,8,12,14,20,26-; heksametil-23,27-epoksi-3H-pirido[2,1-c][1,4]-; oksaazaciklohentriakontin-1,5,11,28,29; (4H,6H,31H)-penton
Klinički podaci
Identifikatori
CAS broj	53123-88-9
ATC kod	L04AA10
PubChem	5284616
DrugBank	DB00877
ChemSpider	10482078
UNII	W36ZG6FT64
KEGG	D00753
ChEBI	CHEBI:9168
ChEMBL	CHEMBL413
Hemijski podaci
Formula	C51H79NO13
Mol. masa	914,172 g/mol
SMILES	eMolekuli & PubHem
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 ; Key: QFJCIRLUMZQUOT-HPLJOQBZSA-N
Farmakokinetički podaci
Bioraspoloživost	20%, manje nakon unosa hrane bogate masnoćama
Vezivanje za proteine plazme	92%
Metabolizam	Hepatički
Poluvreme eliminacije	57–63 sata
Izlučivanje	Uglavnom fekalno
Farmakoinformacioni podaci
Licenca	EU EMEA:link, US FDA:link
Trudnoća	C(AU) C(US)
Pravni status	℞-only (SAD)
Način primene	Oralno

Sirolimus (INN/USAN), takođe poznat kao rapamicin, je imunosupresantni lek koji se koristi za prevenciju odvacivanja transplanta organa. On posebno često nalazi primenu kod transplanta bubrega. Ovaj lek sprečava aktivaciju T ćelija i B ćelija putem inhibicije njihovog responsa na interleukin-2 (IL-2). Sirolimus se takođe koristi za oblaganje koronarnog stenta.

Sirolimus je makrolid koji su otkrili brazilski istraživači kao product bakterje Streptomyces hygroscopicus u uzorku zemljišta sa Uskršnjeg ostrva.^[6]^[7] Ovaj lek je FDA odobrila septembra 1999. Preduzeće Pfizer ga prodaje pod imenom Rapamun.

Sirolimus je originalno razivijen kao antifungalni agens. Međutim, ta forma upotrebe se nije održala jer je otkriveno da ima potentna imunosupresivna i antiproliferativna svojstva. Pokazano je da produžava životni vek miševa, i da verovatno može da bude koristan u lečenju pojedinih formi kancera.

Reference

↑ Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit
↑ Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.
↑ Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit
↑ Joanne Wixon, Douglas Kell (2000). „Website Review: The Kyoto Encyclopedia of Genes and Genomes — KEGG”. Yeast 17 (1): 48–55. DOI:10.1002/(SICI)1097-0061(200004)17:1<48::AID-YEA2>3.0.CO;2-H.
↑ Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594. edit
↑ Vézina C, Kudelski A, Sehgal SN (October 1975). „Rapamycin (AY-22,989), a new antifungal antibiotic”. J. Antibiot. 28 (10): 721–6. DOI:10.7164/antibiotics.28.721. PMID 1102508.
↑ Pritchard DI (2005). „Sourcing a chemical succession for cyclosporin from parasites and human pathogens”. Drug Discovery Today 10 (10): 688–691. DOI:10.1016/S1359-6446(05)03395-7. PMID 15896681.

Vanjske veze

	Portal Medicina
	Portal Hemija

Rapamune official website Arhivirano 2005-08-29 na Wayback Machine-u
Rapamycin bound to proteins in the PDB

[1] Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit

[2] Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.

[3] Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit

[4] Joanne Wixon, Douglas Kell (2000). „Website Review: The Kyoto Encyclopedia of Genes and Genomes — KEGG”. Yeast 17 (1): 48–55. DOI:10.1002/(SICI)1097-0061(200004)17:1<48::AID-YEA2>3.0.CO;2-H.

[5] Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594. edit

[Vezi-6] Vézina C, Kudelski A, Sehgal SN (October 1975). „Rapamycin (AY-22,989), a new antifungal antibiotic”. J. Antibiot. 28 (10): 721–6. DOI:10.7164/antibiotics.28.721. PMID 1102508.

[RapamycinOrigin-7] Pritchard DI (2005). „Sourcing a chemical succession for cyclosporin from parasites and human pathogens”. Drug Discovery Today 10 (10): 688–691. DOI:10.1016/S1359-6446(05)03395-7. PMID 15896681.

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