voclosporin 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
ciclosporin derivatives 4366 515814-01-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • lupkynis
  • trans-R 1524
  • R-1524
  • orelvo
  • voclera
  • ISATX247
  • ISA-247
  • ISA247
  • ISA 247
  • voclosporin
Voclosporin is a calcineurin-inhibitor immunosuppressant. The mechanism of voclosporin suppression of calcineurin has not been fully established. Activation of lymphocytes involves an increase in intracellular calcium concentrations that bind to the calcineurin regulatory site and activate calmodulin binding catalytic subunit and through dephosphorylation activates the transcription factor, Nuclear Factor of Activated T-Cell Cytoplasmic (NFATc). The immunosuppressant activity results in inhibition of lymphocyte proliferation, T-cell cytokine production, and expression of T-cell activation surface antigens.
  • Molecular weight: 1214.65
  • Formula: C63H111N11O12
  • CLOGP: 12
  • LIPINSKI: 3
  • HAC: 23
  • HDO: 5
  • TPSA: 278.80
  • ALOGS: -5.48
  • ROTB: 16
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
47.40 mg O

ADMET properties:

None

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 4.060 Moderate 0.77
caco2-efflux Caco-2 efflux ratio (BA/AB) 18.923 Moderate 0.77
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 10.162 10^-6 cm/s Moderate 0.77
dh-clint Dog hepatocyte intrinsic clearance 41.783 uL/min/10^6 cells Moderate 0.77
dppb Dog plasma protein binding (% unbound) 1.850 % Moderate 0.77
fcs-ppb Fetal calf serum protein binding (% unbound) 4.050 % Moderate 0.77
herg hERG pIC50 4.295 pIC50 Moderate 0.77
hh-clint Human hepatocyte intrinsic clearance 4.592 uL/min/10^6 cells Moderate 0.77
hlm-clint Human liver microsomal intrinsic clearance 18.621 uL/min/mg protein Moderate 0.77
hppb Human plasma protein binding (% unbound) 3.570 % Moderate 0.77
kinase-safety-class EIF2AK3,GRK2,PDK1,PDK2,PDK4 5
kinase-selectivity-class PDK1 1
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 50.234 High 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 24.434 Moderate 0.77
mh-clint Mouse hepatocyte intrinsic clearance 9.036 Moderate 0.77
mppb Mouse plasma protein binding (% unbound) 1 Moderate 0.77
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 226.986 Moderate 0.77
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pld-class Phospholipidosis risk class (1 = positive, 0 = negative) 1 High 0.88
pppb Pig plasma protein binding (% unbound) 0.770 % Moderate 0.77
rat-kpuu-brain Rat brain Kpuu 0.005 % High 0.88
rh-clint Rat hepatocyte intrinsic clearance 11.298 uL/min/10^6 cells Moderate 0.77
rh-fuinc Rat hepatocyte fraction unbound in incubation 8.310 % Moderate 0.77
rppb Rat plasma protein binding (% unbound) 1.510 % Moderate 0.77
solubility-dd Solubility at pH 7.4 in DMSO 82.224 uM Moderate 0.77

Approvals:

DateAgencyCompanyOrphan
Jan. 22, 2021 FDA AURINIA PHARMA U.S.
Sept. 15, 2022 EMA OTSUKA PHARMACEUTICAL NETHERLANDS B.V.

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Urine protein/creatinine ratio increased 782.32 39.28 112 3361 900 90624074
Proteinuria 674.81 39.28 160 3313 23131 90601843
Glomerular filtration rate decreased 621.29 39.28 141 3332 16791 90608183
Blood creatinine increased 210.56 39.28 94 3379 101292 90523682
Therapy interrupted 169.97 39.28 66 3407 50042 90574932
Hypertension 155.98 39.28 133 3340 457399 90167575
Blood pressure increased 149.05 39.28 93 3380 197124 90427850
Absence of immediate treatment response 106.60 39.28 12 3461 4 90624970
Treatment noncompliance 91.54 39.28 43 3430 51684 90573290
Renal impairment 90.41 39.28 54 3419 105367 90519607
Herpes simplex colitis 76.18 39.28 11 3462 93 90624881
Double stranded DNA antibody positive 66.80 39.28 12 3461 430 90624544
Urine albumin/creatinine ratio increased 64.00 39.28 12 3461 546 90624428
Urine abnormality 52.17 39.28 17 3456 7720 90617254
Complement factor C3 decreased 50.52 39.28 9 3464 307 90624667
Urine protein/creatinine ratio abnormal 43.35 39.28 6 3467 36 90624938
Protein urine present 41.70 39.28 14 3459 6970 90618004
Headache 41.06 39.28 97 3376 862649 89762325

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Proteinuria 172.82 62.28 41 395 22942 42597957
Urine protein/creatinine ratio increased 151.84 62.28 22 414 795 42620104
Glomerular filtration rate decreased 116.45 62.28 28 408 16323 42604576
Hypertension 79.93 62.28 37 399 167167 42453732

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Urine protein/creatinine ratio increased 656.14 38.50 95 2413 1478 110585313
Glomerular filtration rate decreased 508.51 38.50 120 2388 28836 110557955
Proteinuria 464.99 38.50 119 2389 39899 110546892
Hypertension 153.58 38.50 111 2397 509973 110076818
Blood creatinine increased 147.28 38.50 75 2433 182814 110403977
Blood pressure increased 128.21 38.50 77 2431 258296 110328495
Therapy interrupted 96.99 38.50 38 2470 49784 110537007
Herpes simplex colitis 79.93 38.50 11 2497 114 110586677
Treatment noncompliance 64.62 38.50 32 2476 72958 110513833
Urine albumin/creatinine ratio increased 62.02 38.50 12 2496 1101 110585690
Double stranded DNA antibody positive 56.86 38.50 10 2498 542 110586249
Absence of immediate treatment response 55.74 38.50 6 2502 3 110586788
Urine abnormality 53.87 38.50 16 2492 9080 110577711
Renal impairment 45.19 38.50 36 2472 188409 110398382
Complement factor C3 decreased 39.90 38.50 7 2501 374 110586417
Systemic lupus erythematosus 39.62 38.50 38 2470 254300 110332491

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L04AD03 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
IMMUNOSUPPRESSANTS
IMMUNOSUPPRESSANTS
Calcineurin inhibitors
FDA EPC N0000175457 Calcineurin Inhibitor Immunosuppressant
FDA MoA N0000175458 Calcineurin Inhibitors
FDA MoA N0000185503 P-Glycoprotein Inhibitors
FDA MoA N0000190107 Organic Anion Transporting Polypeptide 1B1 Inhibitors
FDA MoA N0000190108 Organic Anion Transporting Polypeptide 1B3 Inhibitors

Related Drugs by ATC class:

L04AD Calcineurin inhibitors 2 drugs
ciclosporintacrolimus

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Lupus nephritis indication 68815009
Noninfectious Uveitis indication




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
7.9MG LUPKYNIS AURINIA N213716 Jan. 22, 2021 RX CAPSULE ORAL 7332472 Oct. 17, 2027 TREATMENT OF PATIENTS WITH ACTIVE LUPUS NEPHRITIS
7.9MG LUPKYNIS AURINIA N213716 Jan. 22, 2021 RX CAPSULE ORAL 10286036 Dec. 7, 2037 TREATMENT OF PATIENTS WITH ACTIVE LUPUS NEPHRITIS
7.9MG LUPKYNIS AURINIA N213716 Jan. 22, 2021 RX CAPSULE ORAL 11622991 Dec. 7, 2037 TREATMENT OF PATIENTS WITH ACTIVE LUPUS NEPHRITIS

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
7.9MG LUPKYNIS AURINIA N213716 Jan. 22, 2021 RX CAPSULE ORAL Jan. 22, 2026 NEW CHEMICAL ENTITY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Peptidyl-prolyl cis-trans isomerase A Enzyme INHIBITOR Kd 7.82 IUPHAR

External reference:

IDSource
D09033 KEGG_DRUG
4040008 VANDF
C2607219 UMLSCUI
CHEMBL5314379 ChEMBL_ID
DB11693 DRUGBANK_ID
C484071 MESH_SUPPLEMENTAL_RECORD_UI
11388 IUPHAR_LIGAND_ID
8889 INN_ID
2PN063X6B1 UNII
6918486 PUBCHEM_CID
2475166 RXNORM
343010 MMSL
39286 MMSL
d09707 MMSL
018620 NDDF
1149151008 SNOMEDCT_US
1149188006 SNOMEDCT_US
CHEBI:135957 CHEBI
2PN063X6B1 INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
LUPKYNIS HUMAN PRESCRIPTION DRUG LABEL 1 75626-001 CAPSULE 7.90 mg ORAL NDA 33 sections
LUPKYNIS HUMAN PRESCRIPTION DRUG LABEL 1 75626-001 CAPSULE 7.90 mg ORAL NDA 33 sections