Zotarolimus

Zotarolimus is a macrocyclic lactone immunosuppressant and a derivative of rapamycin (Cay-13346). 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.Formal Name: (42S)-42-deoxy-42-(1H-tetrazol-1-yl)-rapamycin. CAS Number: 221877-54-9. Synonyms: A-179578, ABT-578. Molecular Formula: C52H79N5O12. Formula Weight: 966.2. Purity: >95% (mixture of isomers). Formulation: (Request formulation change), A solid. Solubility: DMF: 15mg/mL, DMSO: 15mg/mL, Ethanol: 20mg/mL, Ethanol:PBS (pH 7.2) (1:3): 0.25mg/mL. SMILES: O=C([C@H](OC)[C@@H](/C(C)=C/[C@@H](C)C(C[C@]([H])(OC([C@]1([H])CCCCN12)=O)[C@@H](C[C@@H]3CC[C@@](N4C=NN=N4)([H])[C@H](OC)C3)C)=O)O)[C@@H](C[C@@H](/C=C/C=C/C=C(C)/[C@H](C[C@@]5([H])O[C@](C(C2=O)=O)(O)[C@H](C)CC5)OC)C)C. 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. InChi Key: CGTADGCBEXYWNE-JUKNQOCSSA-N.