Details of the Drug

General Information of Drug (ID: DMSLJP4)

Drug Name
Ziconotide
Synonyms
Prialt; Ziconotide [USAN]; SNX 111; DRG-0250; Omega-Conotoxin M VIIA; Omega-conotoxin MVIIA; Prialt (TN); SNX-111; Omega-ConopeptideMVIIA (Conus); Omega-Conotoxin mviia, conus magus; Omega-Conotoxin M VIIA (reduced), cyclic (1-16),(8-20),(15-25)-tris(disulfide)
Indication
Disease Entry ICD 11 Status REF
Pain MG30-MG3Z Approved [1]
Traumatic brain injury NA07.Z Phase 1/2 [1]
Chronic pain MG30 Investigative [2]
Therapeutic Class
Analgesics
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 5 Molecular Weight (mw) 2639.2
Logarithm of the Partition Coefficient (xlogp) -14
Rotatable Bond Count (rotbonds) 40
Hydrogen Bond Donor Count (hbonddonor) 42
Hydrogen Bond Acceptor Count (hbondacc) 46
ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 83.6-608 mcgh/L [3]
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 16.4-132 mcg/L [3]
Clearance
The clearance of drug is 0.38 +/- 0.56 mL/min [3]
Elimination
less than 1% of drug is recovered in urine [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 3.7 - 5.5 hours [3]
Metabolism
The drug is metabolized via various peptidases upon entering systemic circulation [3]
Unbound Fraction
The unbound fraction of drug in plasma is 0.5% [4]
Vd
The volume of distribution (Vd) of drug is 0.155 +/- 0.263 L [3]
Chemical Identifiers
Formula
C102H172N36O32S7
IUPAC Name
2-[(1R,4S,7S,13S,16R,21R,24S,27S,30S,33S,36S,39S,42R,45S,48S,54S,60S,63R,68R,71S,77S)-63-amino-13,45,54,60-tetrakis(4-aminobutyl)-4,36-bis(3-carbamimidamidopropyl)-16-carbamoyl-71-[(1R)-1-hydroxyethyl]-7,39,77-tris(hydroxymethyl)-27-[(4-hydroxyphenyl)methyl]-48-methyl-33-(2-methylpropyl)-30-(2-methylsulfanylethyl)-2,5,8,11,14,23,26,29,32,35,38,41,44,47,50,53,56,59,62,69,72,75,78,85-tetracosaoxo-18,19,65,66,81,82-hexathia-3,6,9,12,15,22,25,28,31,34,37,40,43,46,49,52,55,58,61,70,73,76,79,84-tetracosazatricyclo[40.37.4.221,68]pentaoctacontan-24-yl]acetic acid
Canonical SMILES
C[C@H]1C(=O)N[C@H](C(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@H](C(=O)NCC(=O)N1)CCCCN)CCCCN)N)C(=O)N[C@H](C(=O)NCC(=O)N[C@H](C(=O)N3)CO)[C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC2=O)CO)CCCNC(=N)N)CC(C)C)CCSC)CC4=CC=C(C=C4)O)CC(=O)O)C(=O)N)CCCCN)CO)CCCNC(=N)N)CCCCN
InChI
InChI=1S/C102H172N36O32S7/c1-50(2)34-63-91(161)127-62(26-33-171-5)90(160)129-64(35-53-22-24-54(143)25-23-53)92(162)130-65(36-78(148)149)93(163)135-72-48-175-173-45-69(80(108)150)133-86(156)58(18-8-12-29-105)121-76(146)39-117-85(155)66(41-139)131-88(158)61(21-15-32-114-102(111)112)126-96(166)70-46-176-177-47-71(97(167)132-68(43-141)95(165)125-60(87(157)128-63)20-14-31-113-101(109)110)134-89(159)59(19-9-13-30-106)123-81(151)51(3)119-74(144)37-115-83(153)56(16-6-10-27-103)120-75(145)38-116-84(154)57(17-7-11-28-104)124-82(152)55(107)44-172-174-49-73(137-98(72)168)99(169)138-79(52(4)142)100(170)118-40-77(147)122-67(42-140)94(164)136-70/h22-25,50-52,55-73,79,139-143H,6-21,26-49,103-107H2,1-5H3,(H2,108,150)(H,115,153)(H,116,154)(H,117,155)(H,118,170)(H,119,144)(H,120,145)(H,121,146)(H,122,147)(H,123,151)(H,124,152)(H,125,165)(H,126,166)(H,127,161)(H,128,157)(H,129,160)(H,130,162)(H,131,158)(H,132,167)(H,133,156)(H,134,159)(H,135,163)(H,136,164)(H,137,168)(H,138,169)(H,148,149)(H4,109,110,113)(H4,111,112,114)/t51-,52+,55-,56-,57-,58-,59-,60-,61-,62-,63-,64-,65-,66-,67-,68-,69-,70-,71-,72-,73-,79-/m0/s1
InChIKey
BPKIMPVREBSLAJ-QTBYCLKRSA-N
Cross-matching ID
PubChem CID
16135415
ChEBI ID
CHEBI:135912
CAS Number
107452-89-1
DrugBank ID
DB06283
TTD ID
D01NLB
INTEDE ID
DR1728
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Voltage-gated calcium channel alpha Cav2.2 (CACNA1B) TT4FDG6 CAC1B_HUMAN Blocker [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Pain
ICD Disease Classification MG30-MG3Z
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Voltage-gated calcium channel alpha Cav2.2 (CACNA1B) DTT CACNA1B 9.07E-01 7.11E-03 0.06
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 8.31E-01 -4.19E-02 -2.14E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Ziconotide (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Esketamine DMVU687 Moderate Additive CNS depression effects by the combination of Ziconotide and Esketamine. Depression [6A70-6A7Z] [7]
Lasmiditan DMXLVDT Moderate Additive CNS depression effects by the combination of Ziconotide and Lasmiditan. Migraine [8A80] [8]

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2536).
2 Ziconotide FDA Label
3 FDA Approved Drug Products: Prialt (ziconotide) solution
4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 Emerging treatments for traumatic brain injury. Expert Opin Emerg Drugs. 2009 Mar;14(1):67-84.
6 Integrated analysis on the physicochemical properties of dihydropyridine calcium channel blockers in grapefruit juice interactions. Curr Pharm Biotechnol. 2012 Jul;13(9):1705-17.
7 Cerner Multum, Inc. "Australian Product Information.".
8 Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.