Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C52H79N5O12 |
Molecular Weight | 966.21 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 15 / 15 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@]12CC[C@@H](C)[C@@](O)(O1)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O[C@@]([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](C2)OC)[C@H](C)C[C@@H]4CC[C@@H]([C@@H](C4)OC)N5C=NN=N5
InChI
InChIKey=CGTADGCBEXYWNE-JUKNQOCSSA-N
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
DescriptionCurator's Comment: Description was created based on several sources, including
http://www.medscape.com/viewarticle/758919
Curator's Comment: Description was created based on several sources, including
http://www.medscape.com/viewarticle/758919
Zotarolimus (ABT-578) is an immunosuppressant. It is a semi-synthetic derivative of rapamycin. It was designed for use in stents with phosphorylcholine as a carrier. Coronary stents reduce early complications and improve late clinical outcomes in patients needing interventional cardiology. Medtronic are using zotarolimus as the anti-proliferative agent in the polymer coating of their Endeavor and Resolute products. Zotarolimus was developed by Abbott Laboratories as the first cytostatic agent to be used solely for delivery from drug-eluting stents to prevent restenosis. The mechanism (or mechanisms) by which the Endeavor Zotarolimus-Eluting Coronary Stent System affects neointimal production as seen in clinical studies has not been established conclusively. In vitro, zotarolimus inhibited growth factor-induced proliferation of human coronary artery smooth muscle cells and also demonstrated binding affinity with FKBP 12 (binding protein). The suggested mechanism of action of zotarolimus is to bind to FKBP 12, leading to the formation of a trimeric complex with the protein kinase mTOR (mammalian target of rapamycin), inhibiting its activity. Inhibition of mTOR activity leads to inhibition of cell cycle progression from the GI to the S phase.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1902 |
2.8 nM [IC50] | ||
Target ID: GO:0048659 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16449248 |
|||
Target ID: GO:0001935 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16449248 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Endeavor Zotarolimus-Eluting Coronary Stent System Approved UseThe Endeavor Zotarolimus-Eluting Coronary Stent System is indicated for improving coronary luminal diameter in patients with ischemic heart disease due to de novo lesions of length < 27 mm in native coronary arteries with reference vessel diameters of> 2.5 mm to < 3.5 mm. Launch Date2008 |
PubMed
Title | Date | PubMed |
---|---|---|
Zotarolimus, a novel sirolimus analogue with potent anti-proliferative activity on coronary smooth muscle cells and reduced potential for systemic immunosuppression. | 2007 Apr |
|
Rapamycin promotes arterial thrombosis in vivo: implications for everolimus and zotarolimus eluting stents. | 2010 Jan |
Patents
Sample Use Guides
The drug component of the Endeavor Zotarolimus-Eluting Coronary Stent System consists of zotarolimus (the active ingredient) and Phosphorylcholine (PC) polymer (the inactive ingredient).
The Endeavor stent contains 10 ug zotarolimus per millimeter of stent length for all diameters. Because an identical dose (l0 ug/mm zotarolimus per mm stent length) is used for the entire Endeavor 2.5 mm - 3.5 mm diameter range, the total drug per stent is a function of stent length, irrespective of stent diameter.
Route of Administration:
Other
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19567381
Zotarolimus (10(-7) mol/l) enhanced TNF-alpha-induced TF expression by 2.4-fold, which was paralleled by an increase in TF surface activity.
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C574
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C2201
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Zotarolimus
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C82294
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C489443
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ACTIVE MOIETY