voclosporin   Click here for help

GtoPdb Ligand ID: 11388

Synonyms: 1,11-anhydro[L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl- N-methyl-L-valyl-[(2S,3R,4R,6E)-3-hydroxy-4-methyl- 2-(methylamino)nona-6,8-dienoyl][(2S)-2-aminobutanoyl]- N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucine] | E-ISA247 | ISA(TX)247 | ISA-247 | ISA247 | ISATX247 | Lupkynis® | R 1524 | R-1524 | R1524
Approved drug Immunopharmacology Ligand
voclosporin is an approved drug (FDA (2021), EMA (2022))
Compound class: Peptide
Comment: Voclosporin (ISA247, ISATX247) is a cyclic peptide that is a semi-synthetic cyclosporine analogue [1-3,6], but with distinct clinical efficacy and safety profiles [5]. Like cyclosporine, it has immunosuppressive action, and it binds cyclophilin A [4]. Functionally, it acts as a calcineurin inhibitor. Prior to voclosporin, clinically used calcineurin inhibitors were cyclosporine (cyclosporin A), tacrolimus, and pimecrolimus.
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2D Structure
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Canonical SMILES C=C/C=C/C[C@H]([C@H]([C@H]1C(=O)N[C@@H](CC)C(=O)N(C)CC(=O)N(C)[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](C(=O)N([C@H](C(=O)N([C@H](C(=O)N([C@H](C(=O)N1C)C(C)C)C)CC(C)C)C)CC(C)C)C)C)C)O)C
Isomeric SMILES C=C/C=C/C[C@H]([C@H]([C@H]1C(=O)N[C@@H](CC)C(=O)N(C)CC(=O)N(C)[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](C(=O)N([C@H](C(=O)N([C@H](C(=O)N([C@H](C(=O)N1C)C(C)C)C)CC(C)C)C)CC(C)C)C)C)C)O)C
InChI 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
1. Abel MD, Aspeslet LJ, Freitag DG, Naicker S, Trepanier DJ, Kneteman NM, Foster RT, Yatscoff RW. (2001)
ISATX247: a novel calcineurin inhibitor.
J Heart Lung Transplant, 20 (2): 161. [PMID:11250240]
2. Aspeslet L, Freitag D, Trepanier D, Abel M, Naicker S, Kneteman N, Foster R, Yatscoff R. (2001)
ISA(TX)247: a novel calcineurin inhibitor.
Transplant Proc, 33 (1-2): 1048-51. [PMID:11267185]
3. Bîrsan T, Dambrin C, Freitag DG, Yatscoff RW, Morris RE. (2005)
The novel calcineurin inhibitor ISA247: a more potent immunosuppressant than cyclosporine in vitro.
Transpl Int, 17 (12): 767-71. [PMID:15827754]
4. Kuglstatter A, Mueller F, Kusznir E, Gsell B, Stihle M, Thoma R, Benz J, Aspeslet L, Freitag D, Hennig M. (2011)
Structural basis for the cyclophilin A binding affinity and immunosuppressive potency of E-ISA247 (voclosporin).
Acta Crystallogr D Biol Crystallogr, 67 (Pt 2): 119-23. [PMID:21245533]
5. Li Y, Palmisano M, Sun D, Zhou S. (2020)
Pharmacokinetic Disposition Difference Between Cyclosporine and Voclosporin Drives Their Distinct Efficacy and Safety Profiles in Clinical Studies.
Clin Pharmacol, 12: 83-96. [PMID:32669879]
6. (2007)
ISA 247: trans-ISA 247, trans-R 1524, ISA(TX)247, ISAtx 247, ISATx247, LX 211, LX211, R 1524, R-1524.
Drugs R D, 8 (2): 103-12. [PMID:17324008]