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ZOTAROLIMUS

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ZOTAROLIMUS Basic information

Product Name:
ZOTAROLIMUS
Synonyms:
  • ZOTAROLIMUS
  • (42S)-42-Deoxy-42-(1H-tetrazol-1-yl)rapamycin
  • A 179578
  • ABT 578
  • ABT-578;A-179578;ABT578;A179578;ABT 578;A 179578
  • CS-1162
  • Rapamycin, 42-deoxy-42-(1H-tetrazol-1-yl)-, (42S)-
  • Unii-H4gxr80ize
CAS:
221877-54-9
MF:
C52H79N5O12
MW:
966.21
Product Categories:
  • Inhibitors
  • Chiral Reagents
  • Heterocycles
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
Mol File:
221877-54-9.mol
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ZOTAROLIMUS Chemical Properties

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
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Safety Information

HS Code 
29349990
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ZOTAROLIMUS Usage And Synthesis

Description

Zotarolimus is a macrocyclic lactone immunosuppressant and a derivative of rapamycin . 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). 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. Formulations containing zotarolimus have been used in drug-eluting stents in the prevention of restenosis following stent placement.

Chemical Properties

Pale Yellow Solid

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.

Uses

A tetrazole-containing Rapamycin analog as immunomodulator and useful in the treatment of restenosis and immune and autoimmune diseases.

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.

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

ZOTAROLIMUSSupplier

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