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 or derivative
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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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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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
InChI Key BICRTLVBTLFLRD-PTWUADNWSA-N
No information available.
Summary of Clinical Use Click here for help
Voclosporin was advanced to clinical evaluation for autoimmune diseases and the prevention of organ graft rejection. The FDA approved voclosporin (Lupkynis®) in January 2021, as an adjunctive treatment for active lupus nephritis, to be used in combination with a background immunosuppressive therapy. In the EU voclosporin was granted orphan designation (December 2012) as a treatment for non-infectious uveitis.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Calcineurin is a phosphatase that is a key component of immune signalling and which regulates the action of cytotoxic lymphocytes. Drugs that (indirectly) inhibit calcineurin block T cell proliferation and thereby generate their immunosuppressive action.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT00244842 Randomized Placebo-Controlled Study of ISA247 in Plaque Psoriasis Phase 3 Interventional Aurinia Pharmaceuticals Inc.
NCT03597464 Aurinia Renal Assessments 2: Aurinia Renal Response in Lupus With Voclosporin Phase 3 Interventional Aurinia Pharmaceuticals Inc.
NCT03021499 Aurinia Renal Response in Active Lupus With Voclosporin Phase 3 Interventional Aurinia Pharmaceuticals Inc.