Home PI3K/Akt/mTOR mTOR inhibitor - FKBP inhibitor Zotarolimus (ABT-578) For research use only.

Zotarolimus (ABT-578)

Synonyms: A 179578

Zotarolimus (ABT-578,A 179578) is an analogue of rapamycin, and inhibits FKBP-12 binding with IC50 of 2.8 nM.

Zotarolimus (ABT-578) Chemical Structure

Zotarolimus (ABT-578) Chemical Structure

CAS: 221877-54-9

Selleck's Zotarolimus (ABT-578) has been cited by 3 publications

Purity & Quality Control

Batch: Purity: >97%
97

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Biological Activity

Description Zotarolimus (ABT-578,A 179578) 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
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]
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 (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 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.
In Vivo
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]
Animal Research Animal Models Male Sprague-Dawley rats
Dosages 2.5 mg/kg
Administration intravenous or oral
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

Chemical lnformation & Solubility

Molecular Weight 966.21 Formula

C52H79N5O12
CAS No. 221877-54-9 SDF Download Zotarolimus (ABT-578) SDF
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
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (103.49 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble


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