| Identification | Back Directory | [Name]
ZOTAROLIMUS | [CAS]
221877-54-9 | [Synonyms]
ABT 578
CS-1162
Resolute
A 179578
ZOTAROLIMUS
Unii-H4gxr80ize
ZotaroliMus API
Zotarolimus, >
ZotaroliMus, >90%
ZotaroliMus(ABT-578)
ZOTAROLIMUS USP/EP/BP
ZOTAROLIMUS Impurities
42-(1-Tetrazolyl)rapamycin
Zotarolimus
A 179578
(42S)-42-Deoxy-42-(1H-tetrazol-1-yl)rapamycin
42-deoxy-42-(1H-tetrazol-1-yl)-(42S)-Rapamycin
ABT-578;A-179578;ABT578;A179578;ABT 578;A 179578
Rapamycin, 42-deoxy-42-(1H-tetrazol-1-yl)-, (42S)-
(42S)-42-Deoxy-42-(1H-tetrazol-1-yl)rapamycin Zotarolimus(ABT-578) A 179578 Resolute | [Molecular Formula]
C52H79N5O12 | [MDL Number]
MFCD09752954 | [MOL File]
221877-54-9.mol | [Molecular Weight]
966.21 |
| Chemical Properties | Back Directory | [Melting point ]
100-105°C | [Boiling point ]
1016.2±75.0 °C(Predicted) | [density ]
1.25 | [storage temp. ]
Hygroscopic, -20°C Freezer, Under Inert Atmosphere | [solubility ]
DMSO, Methanol (Slightly) | [form ]
Solid | [pka]
10.40±0.70(Predicted) | [color ]
White to Pale Yellow |
| Hazard Information | Back Directory | [Description]
Zotarolimus is a macrocyclic lactone immunosuppressant and a derivative of rapamycin (Item No. 13346).1,2 It binds to FKBP prolyl isomerase 1A (FKBP12; IC50 = 2.57 nM) and inhibits proliferation of human peripheral blood mononuclear cells (PBMCs), rat splenocytes, and human coronary artery smooth muscle cells (IC50s = 7, 1,337, and 0.8 nM, respectively).2 Zotarolimus has immunosuppressive activity in a one-way mixed lymphocyte reaction using human or rat lymphocytes (IC50s = 1.2 and 1,465 nM, respectively). It also reduces symptom severity in a rat model of experimental autoimmune encephalomyelitis (EAE; ED50 = 1.17 mg/kg per day) and delays cardiac allograft rejection in rats (ED50 = 3.71 mg/kg per day). Zotarolimus inhibits neointimal formation and reduces stenosis in pig coronary arteries when applied at 10 μg/mm to stainless steel balloon expandable stents with phosphorylcholine in a model of restenosis.1 Formulations containing zotarolimus have been used in drug-eluting stents in the prevention of restenosis following stent placement. | [Chemical Properties]
Pale Yellow Solid | [Uses]
A tetrazole-containing Rapamycin analog as immunomodulator and useful in the treatment of restenosis and immune and autoimmune diseases. | [Uses]
Zotarolimus is a semi-synthetic macrocyclic lactone prepared from rapamycin by preparation of the 42-triflate ester, followed by displacement with tetrazole and purification of the two isomeric products. This structural change affords a less bioavailable product, a preferred profile for some applications. Like all tacrolimus analogues, zotarolimus binds to a receptor protein (FKBP12). The complex then binds to preventing it from interacting with target proteins. Zotarolimus is extensively cited in the literature with over 200 citations. | [Definition]
ChEBI: Zotarolimus is a macrolide and a lactam. | [in vivo]
Zotarolimus (0.1-10 mg/kg; oral administration; on days 1, 4, 5, 6, and 7) inhibits the rat adjuvant-induced delayed-type hypersensitivity (DTH) response in a dose-dependent manner with an?ED50?value of 1.72 mg/kg/day in the rat adjuvant DTH model[1].
Zotarolimus (0.1-10 mg/kg; oral administration; once daily; for 13 days) inhibits the rat experimental autoimmune encephalomyelitis (EAE) in a dose - dependent manner with an?ED50?value of 1.17 mg/kg/day in the rat EAE model[1].
Zotarolimus (0.1-10 mg/kg; oral administration; once daily; for 13 days) shows a dose-related delay in cardiac allograft rejection with an?ED50?value of 3.71 mg/kg/day in the rat cardiac allograft rejection model[1].
| Animal Model: | Male Sprague-Dawley rats (about 130 g) induced delayed-type hypersensitivity (DTH) model[1]. | | Dosage: | 0.1 mg/kg, 1 mg/kg, 10 mg/kg (10% ethanol, 40% propylene glycol, and 50% of a mixture of 4% cremophor EL in D5W (EPC)) | | Administration: | Oral administration, on days 1, 4, 5, 6, and 7 | | Result: | Inhibited the rat adjuvant-induced DTH response in a dose-dependent manner. |
| Animal Model: | Male Lewis rats (about 220 g) bearing autoimmune encephalomyelitis (EAE)[1]. | | Dosage: | 0.1 mg/kg, 1 mg/kg, 10 mg/kg | | Administration: | Oral administration, once daily, for 13 days | | Result: | Inhibited the rat EAE in a dose-dependent manner. |
| Animal Model: | Lewis rats bearing heterotopic ear-heart transplant[1]. | | Dosage: | 0.1 mg/kg, 1 mg/kg, 10 mg/kg | | Administration: | Oral administration, once daily, for 13 days | | Result: | Caused a dose-related delay in cardiac allograft rejection. |
| [storage]
Store at -20°C | [References]
[1] ROBIN COLLINGWOOD. Stent-based delivery of ABT-578 via a phosphorylcholine surface coating reduces neointimal formation in the porcine coronary model[J]. Catheterization and Cardiovascular Interventions, 2005, 65 2: 227-232. DOI: 10.1002/ccd.20348
[2] YUNG-WU CHEN. Zotarolimus, a novel sirolimus analogue with potent anti-proliferative activity on coronary smooth muscle cells and reduced potential for systemic immunosuppression.[J]. Journal of Cardiovascular Pharmacology, 2007, 49 4: 228-235. DOI: 10.1097/fjc.0b013e3180325b0a |
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