ZOTAROLIMUS

ZOTAROLIMUS Property

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

Safety

HS Code 

29349990

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P312Call a POISON CENTER or doctor/physician if you feel unwell.

P321Specific treatment (see … on this label).

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P337+P313IF eye irritation persists: Get medical advice/attention.

P362Take off contaminated clothing and wash before reuse.

P403+P233Store in a well-ventilated place. Keep container tightly closed.

P405Store locked up.

P501Dispose of contents/container to..…

ZOTAROLIMUS Chemical Properties,Usage,Production

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

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