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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
Structure of ZOTAROLIMUS

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

HIDE SMILES / InChI

Description
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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Endeavor Zotarolimus-Eluting Coronary Stent System

Approved Use

The 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 Date

2008
PubMed

PubMed

TitleDatePubMed
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

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
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.
Name Type Language
ZOTAROLIMUS
INN   MART.   USAN   WHO-DD  
USAN   INN  
Official Name English
Zotarolimus [WHO-DD]
Common Name English
MDT-4107
Code English
ZOTAROLIMUS [MART.]
Common Name English
ZOTAROLIMUS [USAN]
Common Name English
ABT-578
Code English
zotarolimus [INN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C574
Created by admin on Fri Dec 15 16:02:06 GMT 2023 , Edited by admin on Fri Dec 15 16:02:06 GMT 2023
NCI_THESAURUS C2201
Created by admin on Fri Dec 15 16:02:06 GMT 2023 , Edited by admin on Fri Dec 15 16:02:06 GMT 2023
Code System Code Type Description
PUBCHEM
9876378
Created by admin on Fri Dec 15 16:02:06 GMT 2023 , Edited by admin on Fri Dec 15 16:02:06 GMT 2023
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DRUG CENTRAL
2949
Created by admin on Fri Dec 15 16:02:06 GMT 2023 , Edited by admin on Fri Dec 15 16:02:06 GMT 2023
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ChEMBL
CHEMBL1614661
Created by admin on Fri Dec 15 16:02:06 GMT 2023 , Edited by admin on Fri Dec 15 16:02:06 GMT 2023
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CAS
221877-54-9
Created by admin on Fri Dec 15 16:02:06 GMT 2023 , Edited by admin on Fri Dec 15 16:02:06 GMT 2023
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SMS_ID
100000124446
Created by admin on Fri Dec 15 16:02:06 GMT 2023 , Edited by admin on Fri Dec 15 16:02:06 GMT 2023
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EPA CompTox
DTXSID50873387
Created by admin on Fri Dec 15 16:02:06 GMT 2023 , Edited by admin on Fri Dec 15 16:02:06 GMT 2023
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WIKIPEDIA
Zotarolimus
Created by admin on Fri Dec 15 16:02:06 GMT 2023 , Edited by admin on Fri Dec 15 16:02:06 GMT 2023
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NCI_THESAURUS
C82294
Created by admin on Fri Dec 15 16:02:06 GMT 2023 , Edited by admin on Fri Dec 15 16:02:06 GMT 2023
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EVMPD
SUB32090
Created by admin on Fri Dec 15 16:02:06 GMT 2023 , Edited by admin on Fri Dec 15 16:02:06 GMT 2023
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USAN
QQ-84
Created by admin on Fri Dec 15 16:02:06 GMT 2023 , Edited by admin on Fri Dec 15 16:02:06 GMT 2023
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FDA UNII
H4GXR80IZE
Created by admin on Fri Dec 15 16:02:06 GMT 2023 , Edited by admin on Fri Dec 15 16:02:06 GMT 2023
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INN
8644
Created by admin on Fri Dec 15 16:02:06 GMT 2023 , Edited by admin on Fri Dec 15 16:02:06 GMT 2023
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MESH
C489443
Created by admin on Fri Dec 15 16:02:06 GMT 2023 , Edited by admin on Fri Dec 15 16:02:06 GMT 2023
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