Voclosporin

Voclosporin is an immunosuppressant and a derivative of cyclosporin A (Cay-12088). It binds to cyclophilin A (Kd = 15 nM) and inhibits calcineurin activity in isolated human whole blood (IC50 = 120 ng/ml). Voclosporin reduces the proliferation of, and production of IL-2, IFN-gamma, and TNF-alpha in, isolated cynomolgus monkey lymphocytes (EC50s = 202.79, 135.32, 177.11, and 138.56 ng/ml, respectively). It decreases disease severity in a rat model of experimental autoimmune uveoretinitis induced by interphotoreceptor retinoid-binding protein (IRBP), also known as retinoid binding protein 3 (RBP3), when administered at doses ranging from 2.5 to 40 mg/kg. Voclosporin (1.75 mg/kg) increases graft survival in a rat model of heterotopic heart transplantation. Unlike cyclosporin A, voclosporin does not increase serum creatinine levels in rabbits. Voclosporin also inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in infected Calu-3 cells in a concentration-dependent manner. Formulations containing voclosporin have been used in the treatment of lupus nephritis.Formal Name: 6-[(2S,3R,4R,6E)-3-hydroxy-4-methyl-2-(methylamino)-6,8-nonadienoic acid]-cyclosporin A. CAS Number: 515814-01-4. Synonyms: (E)-ISA247, ISATX247, LX211, R-15424, trans-ISA 247. Molecular Formula: C63H111N11O12. Formula Weight: 1214.6. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: Methanol: Soluble. SMILES: C=C/C=C/C[C@@H](C)[C@H]([C@]1([H])N(C([C@@H](N(C([C@@H](N(C([C@@H](N(C([C@H](NC([C@@H](NC([C@@H](N(C([C@@H](NC([C@@H](N(C(CN(C([C@@H](NC1=O)CC)=O)C)=O)C)CC(C)C)=O)C(C)C)=O)C)CC(C)C)=O)C)=O)C)=O)C)CC(C)C)=O)C)CC(C)C)=O)C)C(C)C)=O)C)O. InChi Code: InChI=1S/C63H111N11O12/c1-25-27-28-29-41(15)53(76)52-57(80)66-44(26-2)59(82)68(18)34-49(75)69(19)45(30-35(3)4)56(79)67-50(39(11)12)62(85)70(20)46(31-36(5)6)55(78)64-42(16)54(77)65-43(17)58(81)71(21)47(32-37(7)8)60(83)72(22)48(33-38(9)10)61(84)73(23)51(40(13)14)63(86)74(52)24/h25,27-28,35-48,50-53,76H,1,26,29-34H2,2-24H3,(H,64,78)(H,65,77)(H,66,80)(H,67,79)/b28-27+/t41-,42+,43-,44+,45+,46+,47+,48+,50+,51+,52+,53-/m1/s1. InChi Key: BICRTLVBTLFLRD-PTWUADNWSA-N.