Voclosporin

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Voclosporin
Accession Number
DB11693  (DB04906)
Type
Small Molecule
Groups
Investigational
Description

Voclosporin is a novel cyclosporine analog and immunosuppressive compound currently being investigated for the treatment of psoriasis and for the prevention of organ rejection in kidney transplant patients. All studies to date suggest that Voclosporin is more potent and less toxic than currently available treatments within the drug class of calcineurin inhibitors.

Structure
Thumb
Synonyms
Not Available
External IDs
ISA-247 / ISA247 / ISATX-247 / ISATX247 / LX-211 / LX211
Categories
UNII
2PN063X6B1
CAS number
515814-01-4
Weight
Average: 1214.646
Monoisotopic: 1213.841368058
Chemical Formula
C63H111N11O12
InChI Key
BICRTLVBTLFLRD-PTWUADNWSA-N
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
IUPAC Name
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-ethyl-33-[(1R,2R,4E)-1-hydroxy-2-methylhepta-4,6-dien-1-yl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-bis(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecaazacyclotritriacontan-2,5,8,11,14,17,20,23,26,29,32-undecone
SMILES
CC[[email protected]@H]1NC(=O)[[email protected]]([[email protected]](O)[[email protected]](C)C\C=C\C=C)N(C)C(=O)[[email protected]](C(C)C)N(C)C(=O)[[email protected]](CC(C)C)N(C)C(=O)[[email protected]](CC(C)C)N(C)C(=O)[[email protected]@H](C)NC(=O)[[email protected]](C)NC(=O)[[email protected]](CC(C)C)N(C)C(=O)[[email protected]@H](NC(=O)[[email protected]](CC(C)C)N(C)C(=O)CN(C)C1=O)C(C)C

Pharmacology

Indication
Not Available
Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

Voclosporin inhibits calcineurin. As a consequence, it inhibits T cell activation by blocking the transcription of early cytokines.

TargetActionsOrganism
UCalcineurin subunit B type 1Not AvailableHuman
UCalcineurin subunit B type 2Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Voclosporin.Investigational
Clostridium tetani toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Clostridium tetani toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Voclosporin.Approved
Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Voclosporin.Approved
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Voclosporin.Approved
FingolimodVoclosporin may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Voclosporin.Investigational
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Voclosporin.Investigational
Hepatitis A VaccineThe therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Voclosporin.Approved
Hepatitis B Vaccine (Recombinant)The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Voclosporin.Approved, Withdrawn
INGN 201The therapeutic efficacy of INGN 201 can be decreased when used in combination with Voclosporin.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Voclosporin.Investigational
LeflunomideThe risk or severity of adverse effects can be increased when Voclosporin is combined with Leflunomide.Approved, Investigational
NatalizumabThe risk or severity of adverse effects can be increased when Voclosporin is combined with Natalizumab.Approved, Investigational
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Voclosporin.Approved, Investigational
Rabies virus inactivated antigen, AThe risk or severity of adverse effects can be increased when Voclosporin is combined with Rabies virus inactivated antigen, A.Approved
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Voclosporin.Approved
RindopepimutThe therapeutic efficacy of Rindopepimut can be decreased when used in combination with Voclosporin.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Voclosporin.Approved
Rotavirus VaccineThe therapeutic efficacy of Rotavirus Vaccine can be decreased when used in combination with Voclosporin.Approved
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with Voclosporin.Approved
Salmonella typhi ty21a live antigenThe therapeutic efficacy of Salmonella typhi ty21a live antigen can be decreased when used in combination with Voclosporin.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Voclosporin.Approved
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Voclosporin.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Voclosporin.Approved, Investigational
TecemotideThe therapeutic efficacy of Tecemotide can be decreased when used in combination with Voclosporin.Investigational
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Voclosporin.Investigational
TofacitinibVoclosporin may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the neutropenic activities of Voclosporin.Approved, Investigational
Varicella Zoster Vaccine (Live/Attenuated)The therapeutic efficacy of Zoster vaccine can be decreased when used in combination with Voclosporin.Approved
Yellow fever vaccineThe therapeutic efficacy of Yellow fever vaccine can be decreased when used in combination with Voclosporin.Approved
Food Interactions
Not Available

References

General References
  1. Birsan T, Dambrin C, Freitag DG, Yatscoff RW, Morris RE: The novel calcineurin inhibitor ISA247: a more potent immunosuppressant than cyclosporine in vitro. Transpl Int. 2005 May;17(12):767-71. Epub 2005 Apr 13. [PubMed:15827754]
  2. Bissonnette R, Papp K, Poulin Y, Lauzon G, Aspeslet L, Huizinga R, Mayo P, Foster RT, Yatscoff RW, Maksymowych WP: A randomized, multicenter, double-blind, placebo-controlled phase 2 trial of ISA247 in patients with chronic plaque psoriasis. J Am Acad Dermatol. 2006 Mar;54(3):472-8. Epub 2006 Jan 23. [PubMed:16488299]
External Links
PubChem Compound
6918486
PubChem Substance
347828058
ChemSpider
5293683
ChEBI
135957

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentKeratoconjunctivitis Sicca1
1RecruitingTreatmentVolunteers1
2Active Not RecruitingTreatmentNephritis, Lupus1
2CompletedTreatmentKidney Diseases1
2CompletedTreatmentNephritis, Lupus1
3CompletedTreatmentAnterior Uveitis (AU) / Panuveitis1
3CompletedTreatmentNoninfectious Uveitis1
3CompletedTreatmentDiffuse posterior uveitis / Panuveitis / Uveitis, Intermediate2
3CompletedTreatmentPsoriasis3
3RecruitingTreatmentNephritis, Lupus1
3WithdrawnPreventionTransplantation, Renal1
Not AvailableAvailableNot AvailableImmunosuppression / Transplantation, Kidney1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00401 mg/mLALOGPS
logP4.2ALOGPS
logP3.78ChemAxon
logS-5.5ALOGPS
pKa (Strongest Acidic)11.83ChemAxon
pKa (Strongest Basic)-2.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area278.8 Å2ChemAxon
Rotatable Bond Count16ChemAxon
Refractivity331.79 m3·mol-1ChemAxon
Polarizability133.16 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as cyclosporins. These are cyclic depsipeptides containing the cyclosporin backbone.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Peptidomimetics
Sub Class
Peptoid-peptide hybrids
Direct Parent
Cyclosporins
Alternative Parents
Oligopeptides / Macrolactams / Alpha amino acids and derivatives / Tertiary carboxylic acid amides / Secondary carboxylic acid amides / Secondary alcohols / Lactams / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds
show 3 more
Substituents
Cyclosporin-backbone / Alpha-oligopeptide / Macrolactam / Alpha-amino acid or derivatives / Tertiary carboxylic acid amide / Carboxamide group / Lactam / Secondary alcohol / Secondary carboxylic acid amide / Carboxylic acid derivative
show 12 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein domain specific binding
Specific Function
Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity.
Gene Name
PPP3R1
Uniprot ID
P63098
Uniprot Name
Calcineurin subunit B type 1
Molecular Weight
19299.785 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Calcium ion binding
Specific Function
Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity (By similarity).
Gene Name
PPP3R2
Uniprot ID
Q96LZ3
Uniprot Name
Calcineurin subunit B type 2
Molecular Weight
19533.065 Da

Drug created on October 20, 2016 14:40 / Updated on December 01, 2017 16:22