| Size | Price | Stock | Qty |
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| 2mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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Purity: ≥98%
Zotarolimus (also known as ABT-578; A 179578), a tetrazole-based and semi-synthetic analog of rapamycin, is a highly potent immunosuppressant with the potential to be used for preventing coronary artery restenosis. With an IC50 of 2.8 nM, it prevents FKBP-12 binding. Restenosis, immune, and autoimmune diseases may benefit from its use in treatment. With IC50 values of 2.9 and 2.6 nM, respectively, zotarolimus inhibited the proliferation of smooth muscle cells (SMC) and endothelial cells (EC) in human coronary artery cells. Zotarolimus inhibited Con A-induced human and rat T cell proliferation in peripheral blood mononuclear cells (PBMC) and rat splenocytes with IC50 values of 7.0 and 1337 nM, respectively, in a concentration-dependent manner. In lymphocytes derived from humans or rats, zotarolimus inhibited the human and rat mixed lymphocyte reaction (MLR) with IC50 values of 1.2 and 1465 nM respectively in a concentration-dependent way.
| Targets |
FKBP-12 (IC50 = 2.8 nM)
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|---|---|
| ln 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. With IC50 values of 2.9 nM and 2.6 nM for smooth muscle cell and endothelial cell proliferation inhibition, respectively, zotarolimus is very effective.[1] In terms of its mechanism, zatarolimus is comparable to sirolimus in that it binds to the immunophilin FKBP12 with high affinity and has a similar ability to stop the growth of both human and rat T cells in vitro. With an IC50 of 7.0 nM for human T cells and 1337 nM for rat T cells, respectively, zotarolimus inhibits Con A-induced T cell proliferation. [2]
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| ln Vivo |
In a 28-day, thoroughly studied swine model of coronary artery restenosis, zotarolimus-eluting stents effectively reduce neointima formation. When compared to bare metal stents (15.4% with the Driver stent to 8.1% with the Endeavor stent), zotarolimus appears to be effective at preventing neointimal thickening, lowering late loss from 1.03 to 0.62 mm and lowering TVF by 47%. [1] With respective ED50 values of 1.72, 1.17, and 3.71 mg/kg/day, zotarolimus is effective in preventing adjuvant DTH, EAE, and cardiac allograft rejection. [2]
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| Enzyme Assay |
Following the addition of 50 μL/well of buffer A (2% BSA and 0.2% Tween-20 in D-PBS) for 30–60 min, 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. The following step involves washing the microtiter plates three times with buffer B (0.2% Tween in D-PBS, pH adjusted to 7.4). A-79397 (an FK506 analogue)-alkaline phosphatase conjugate in buffer A is added to each well after 50 μL of buffer A (for maximum), 20 M FK506 in buffer A (for background), or various concentrations of zotarolimus (10 pM-1 M) in buffer A are added to each well. Three washes with buffer B are performed after the microtiter plates have been incubated at room temperature for 2-2.5 hours.
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| Cell Assay |
In vitro tritiated thymidine incorporation is used to assess cell proliferation. The desired density of hCa (5000 hCaSMC; 10,000 hCaEC) human coronary artery cells is applied to 96-well plates in complete media after being seeded into tissue culture flasks for expansion. In order to synchronize cells and induce G0 state, complete media is replaced with incomplete media after two days. 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) of3H-thymidine are added to each well. The cells are incubated at 37°C for 16-18 h to allow for incorporation of3H-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 of3H-thymidine incorporation into newly synthesized DNA relative to cells grown in complete media.
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| Animal Protocol |
Male Sprague-Dawley rats
2.5 mg/kg intravenous or oral |
| References |
| Molecular Formula |
C52H79N5O12
|
|---|---|
| Molecular Weight |
966.21000
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| Exact Mass |
965.5725
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| Elemental Analysis |
C, 64.64; H, 8.24; N, 7.25; O, 19.87
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| CAS # |
221877-54-9
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| Related CAS # |
42-(2-Tetrazolyl)rapamycin;221877-56-1
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| Appearance |
Solid powder
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| SMILES |
C[C@@H]1CC[C@H]2C[C@@H](/C(=C/C=C/C=C\[C@H](C[C@H](C(=O)[C@@H]([C@@H](/C(=C/[C@H](C(=O)C[C@H](OC(=O)[C@@H]3CCCCN3C(=O)C(=O)[C@@]1(O2)O)[C@H](C)C[C@@H]4CC[C@@H]([C@@H](C4)OC)N5C=NN=N5)C)/C)O)OC)C)C)/C)OC
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| InChi Key |
CGTADGCBEXYWNE-JUKNQOCSSA-N
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| InChi Code |
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
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| Chemical Name |
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24Z,26E,28E,30S,32S,35R)-1,18-dihydroxy-19,30-dimethoxy-12-[(2R)-1-[(1S,3R,4S)-3-methoxy-4-(tetrazol-1-yl)cyclohexyl]propan-2-yl]-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone
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| Synonyms |
A 179578; A-179578; A179578; ABT578; ABT-578; ABT 578; Endeavor; Zotarolimus; 42-deoxy-42-(1H-tetrazol-1-yl)-; (42S)-Rapamycin
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~103.5 mM)
Water: <1 mg/mL Ethanol: ~100 mg/mL (~103.5 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (2.59 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.59 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0350 mL | 5.1749 mL | 10.3497 mL | |
| 5 mM | 0.2070 mL | 1.0350 mL | 2.0699 mL | |
| 10 mM | 0.1035 mL | 0.5175 mL | 1.0350 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04825886 | Active Recruiting |
Device: Zotarolimus-Eluting Stent |
Coronary Disease Myocardial Ischemia |
Chonnam National University Hospital |
December 28, 2017 | |
| NCT04937803 | Active Recruiting |
Device: Drug-coated balloon Device: Zotarolimus-Eluting Coronary Stent |
ACS DCB |
Harbin Medical University | April 19, 2021 | |
| NCT02100722 | Active Recruiting |
Procedure: CABG Device: Resolute Onyx Stent |
Coronary Disease Coronary Stenosis |
Stanford University | August 25, 2014 | |
| NCT04192747 | Active Recruiting |
Device: Percutaneous Coronary Intervention |
Coronary Disease Coronary Stenosis |
Elixir Medical Corporation | December 16, 2020 |
Inhibition of FKBP-12 binding by zotarolimus. Eur Heart J, 2006, 27(8), 988-993. |
Inhibition of cultured hCaSMC and hCaEC by zotarolimus. |
Representative histological images of low (×4) and high (×20) power magnification of arteries implanted with zotarolimus-eluting stents (A and C) and control (PC-coated) stents (B and D) after 28 days. |
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