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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

Molecular Formula C52H79N5O12
Molecular Weight 966.21
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 15 / 15
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

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 TargetPharmacologyConditionPotency
2.8 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Endeavor Zotarolimus-Eluting Coronary Stent System

PubMed

Patents

Sample Use Guides

In Vivo Use Guide
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
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.
Substance Class Chemical
Record UNII
H4GXR80IZE
Record Status Validated (UNII)
Record Version