Zotarolimus (ABT-578)

Catalog No.S7091

For research use only.

Zotarolimus (ABT-578) is an analogue of rapamycin, and inhibits FKBP-12 binding with IC50 of 2.8 nM.

Zotarolimus (ABT-578) Chemical Structure

CAS No. 221877-54-9

Selleck's Zotarolimus (ABT-578) has been cited by 1 Publication

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Biological Activity

Description Zotarolimus (ABT-578) is an analogue of rapamycin, and inhibits FKBP-12 binding with IC50 of 2.8 nM.
Features Zotarolimus has a shorter in vivo half-life and is also demonstrated in rats to have less potent systemic immunosuppression than rapamycin.
Targets
FKBP-12 [1]
()
2.8 nM
In vitro

Zotarolimus (ABT-578) is a semi-synthetic analogue of rapamycin, made by substituting a tetrazole ring for the native hydroxyl group at position 42 in rapamycin. Zotarolimus is highly effective in inhibiting both smooth muscle cell and endothelial cell proliferation, with IC50 values of 2.9 nM and 2.6 nM, respectively. [1] Zotarolimus is mechanistically similar to sirolimus in having high-affinity binding to the immunophilin FKBP12 and comparable potency for inhibiting in vitro proliferation of both human and rat T cells. Zotarolimus inhibits Con A-induced human T cells and rat T cells proliferation with IC50 of 7.0 nM and 1337 nM respectively. [2]

In vivo Zotarolimus-eluting stents effectively reduce neointima formation in a 28-day, well-characterized swine model of coronary artery restenosis. Zotarolimus appears effective in preventing neointimal thickening, reducing late loss from 1.03 to 0.62 mm with a 47% reduction in TVF compared with bare metal stents (15.4% with the Driver stent to 8.1% with the Endeavor stent). [1] Zotarolimus is efficacious in suppressing adjuvant DTH, EAE, and cardiac allograft rejection with ED50 values of 1.72, 1.17, and 3.71 mg/kg/day, respectively. [2]

Protocol (from reference)

Kinase Assay:

[1]

  • Binding Affinity to FKBP12:

    96-well microtiter plates are first coated with FKBP-12 CMP-KDO synthetase fusion protein at 10 μg/mL, 100 μL/well for 2-3 h, followed by addition of 50 μL/well of buffer A (2% BSA and 0.2% Tween-20 in D-PBS) for 30-60 min. Microtiter plates are then washed three times with buffer B (0.2% Tween in D-PBS, pH adjusted to 7.4). Fifty microlitres of buffer A (for maximum), 20 μM FK506 in buffer A (for background), or various concentrations of zotarolimus (10 pM-1 μM) in buffer A are added to each well followed by addition of 50 μL of A-79397 (an FK506 analogue)-alkaline phosphatase conjugate in buffer A. Microtiter plates are incubated at room temperature for 2-2.5 h followed by three washes with buffer B. About 100 μL of pNPP (p-nitrophenyl-phosphate) in 0.1 M aminomethylpropanol are added to each well and plates are incubated at room temperature for 90-120 min. Absorbance at 405 nM is read using an ELISA plate

Cell Research:

[1]

  • Cell lines: Human coronary artery cells
  • Concentrations: ~1 μM
  • Incubation Time: 5 days
  • Method:

    Cell proliferation is assayed by measuring tritiated thymidine incorporation in vitro. Human coronary artery cells (hCa) are seeded into tissue culture flasks for expansion and applied to 96-well plates at desired density in complete media (5000 hCaSMC; 10 000 hCaEC). After 2 days, complete media is replaced with incomplete media to synchronize cells and induce G0 state. Two days later, incomplete media are removed and replaced with complete media (serum/growth factors) to induce G0 to G1 transition. Complete media also contain drug at desired concentrations to determine its effects on cell proliferation. On day 7, 3H-thymidine is added to cells to monitor DNA synthesis, and cells are harvested after overnight incorporation of radioactivity. After an incubation period of 72 h, 25 μL (1 μCi/well) of 3H-thymidine are added to each well. The cells are incubated at 37°C for 16-18 h to allow for incorporation of 3H-thymidine into newly synthesized DNA and the cells harvested onto 96-well plates containing bonded glass fibre filters . The filter plates are air-dried overnight, MicroScint-20 (25 μL) added to each filter well and counted. Drug activity is determined by the inhibition of 3H-thymidine incorporation into newly synthesized DNA relative to cells grown in complete media.

Animal Research:

[2]

  • Animal Models: Male Sprague-Dawley rats
  • Dosages: 2.5 mg/kg
  • Administration: intravenous or oral

Solubility (25°C)

In vitro

DMSO 100 mg/mL
(103.49 mM)
Ethanol 100 mg/mL
(103.49 mM)
Water Insoluble

Chemical Information

Molecular Weight 966.21
Formula

C52H79N5O12

CAS No. 221877-54-9
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles 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)N5C=NN=N5)C)C)O)OC)C)C)C)OC

In vivo Formulation Calculator (Clear solution)

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT01239654 Completed Device: stent implantation Acute Coronary Syndrome IRCCS San Raffaele|Mediolanum Cardio Research|Cardiovascular Research Foundation New York September 2010 Phase 3
NCT01003717 Completed -- Coronary Artery Disease Rebecca Torguson|Medstar Health Research Institute October 2009 --
NCT00846846 Completed Device: Endeavor® Zotarolimus Eluting Coronary Stent System Coronary Artery Disease Autosomal Dominant 1 Medtronic Vascular January 2009 Phase 4
NCT00815139 Completed -- Coronary Artery Disease Yonsei University February 2008 --
NCT00599885 Completed Drug: telmisartan|Drug: valsartan Hypertension|Diabetes|Coronary Artery Disease Korea University Anam Hospital September 2007 Phase 4
NCT00476957 Completed Device: Stent Ischemic Heart Disease Medtronic Vascular|Medtronic Bakken Research Center June 2007 Phase 4

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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