Zotarolimus

Zotarolimus
Clinical data
Other names(42S)-42-Deoxy-42-(1H-tetrazol-1-yl)-rapamycin
ATC code
  • None
Identifiers
  • (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-10,21-dimethoxy-3-{(1R)-2-[(1S,3R,4S)-3-methoxy-4-(1H-tetrazol-1-yl)cyclohexyl]-1-methylethyl}-6,8,12,14,20,26-hexamethyl-4,9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-heptadecahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontine-1,5,11,28,29(6H,31H)-pentone
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC52H79N5O12
Molar mass966.227 g·mol−1
3D model (JSmol)
  • CC1CCC2CC(C(=CC=CC=CC(CC(C(=O)C(C(C(=CC(C(=O)CC(OC(=O)C3CCCCN3C(=O)C(=O)C1(O2)O)C(C)CC4CCC(C(C4)OC)n5cnnn5)C)C)O)OC)C)C)C)OC
  • InChI=1S/C52H79N5O12/c1-31-16-12-11-13-17-32(2)43(65-8)28-39-21-19-37(7)52(64,69-39)49(61)50(62)56-23-15-14-18-41(56)51(63)68-44(34(4)26-38-20-22-40(45(27-38)66-9)57-30-53-54-55-57)29-42(58)33(3)25-36(6)47(60)48(67-10)46(59)35(5)24-31/h11-13,16-17,25,30-31,33-35,37-41,43-45,47-48,60,64H,14-15,18-24,26-29H2,1-10H3/b13-11+,16-12+,32-17+,36-25+/t31-,33-,34-,35-,37-,38+,39+,40+,41+,43+,44+,45-,47-,48+,52-/m1/s1
  • Key:CGTADGCBEXYWNE-JUKNQOCSSA-N

Zotarolimus (INN, codenamed ABT-578) is an immunosuppressant. It is a semi-synthetic derivative of sirolimus (rapamycin). It was designed for use in stents with phosphorylcholine as a carrier. Zotarolimus, or ABT-578, was originally used on Abbott's coronary stent platforms to reduce early inflammation and restenosis; however, Zotarolimus failed Abbott's primary endpoint to bring their stent/drug delivery system to market. The drug was sold/distributed to Medtronic for use on their stent platforms, which is the same drug they use today. Coronary stents reduce early complications and improve late clinical outcomes in patients needing interventional cardiology.[1] The first human coronary stent implantation was first performed in 1986 by Puel et al.[1][2] However, there are complications associated with stent use, development of thrombosis which impedes the efficiency of coronary stents, haemorrhagic and restenosis complications are problems associated with stents.[1]

These complications have prompted the development of drug-eluting stents. Stents are bound by a membrane consisting of polymers which not only slowly release zotarolimus and its derivatives into the surrounding tissues but also do not invoke an inflammatory response by the body.

Medtronic are using zotarolimus as the anti-proliferative agent in the polymer coating of their Endeavor and Resolute products.[3]

  1. ^ a b c Braunwald E, Zipes D, Libby P, eds. (2001). Heart diseases: a textbook of cardiovascular disease (6th ed.). Philadelphia: Saunders Elsevier.
  2. ^ Sigwart U, Puel J, Mirkovitch V, Joffre F, Kappenberger L (March 1987). "Intravascular stents to prevent occlusion and restenosis after transluminal angioplasty". The New England Journal of Medicine. 316 (12): 701–6. doi:10.1056/NEJM198703193161201. PMID 2950322.
  3. ^ "Medtronic Receives FDA Approval for Endeavor Zotarolimus-Eluting Coronary Stent System".