Home PI3K/Akt/mTOR mTOR inhibitor Zotarolimus (ABT-578)

research use only

Zotarolimus (ABT-578) mTOR inhibitor

Cat.No.S7091

Zotarolimus (ABT-578, A 179578), an analogue of rapamycin, inhibits FKBP-12 binding with an IC50 of 2.8 nM.
Zotarolimus (ABT-578) mTOR inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 966.21

Jump to

Quality Control

Batch: Purity: >97%
97

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (103.49 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight
Dilution Calculator Molecular Weight Calculator

In vivo
Batch:

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg
g
μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO
%
% Tween 80
% ddH2O
% DMSO
+
%

Calculation results:

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.

Chemical Information, Storage & Stability

Molecular Weight 966.21 Formula

C52H79N5O12

 Storage (From the date of receipt)
CAS No. 221877-54-9 Download SDF Storage of Stock Solutions

Synonyms A 179578 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

Mechanism of Action

Features
Zotarolimus has a shorter in vivo half-life and is also demonstrated in rats to have less potent systemic immunosuppression than rapamycin.
Targets/IC50/Ki
FKBP-12
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. This compound 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. It 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.

Kinase Assay
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 (ABT-578) (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
In vivo

Zotarolimus (ABT-578) effectively reduces neointima formation in a 28-day, well-characterized swine model of coronary artery restenosis. It 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). This compound 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.

References

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01239654 Completed
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
Coronary Artery Disease Autosomal Dominant 1
Medtronic Vascular
 January 2009 Phase 4
NCT00815139 Completed
Coronary Artery Disease
Yonsei University
 February 2008 --
NCT00599885 Completed
Hypertension|Diabetes|Coronary Artery Disease
Korea University Anam Hospital
 September 2007 Phase 4
NCT00476957 Completed
Ischemic Heart Disease
Medtronic Vascular|Medtronic Bakken Research Center
 June 2007 Phase 4

Tech Support

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

Signaling Pathway Map