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], [2]
Traumatic brain injury	NA07.Z	Phase 1/2	[1], [3]

Therapeutic Class

Analgesics

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 5

Molecular Weight (mw)

2639.2

Topological Polar Surface Area (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 [4]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 16.4-132 mcg/L [4]
Clearance: The clearance of drug is 0.38 +/- 0.56 mL/min [4]
Elimination: less than 1% of drug is recovered in urine [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 3.7 - 5.5 hours [4]
Metabolism: The drug is metabolized via various peptidases upon entering systemic circulation [4]
Unbound Fraction: The unbound fraction of drug in plasma is 0.5% [5]
Vd: The volume of distribution (Vd) of drug is 0.155 +/- 0.263 L [4]

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

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	[3]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[6]

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Molecular Interaction Atlas (MIA)

MIA Detail

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)

MEA Detail

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]	[26]
Lasmiditan	DMXLVDT	Moderate	Additive CNS depression effects by the combination of Ziconotide and Lasmiditan.	Migraine [8A80]	[27]
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References

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3	Emerging treatments for traumatic brain injury. Expert Opin Emerg Drugs. 2009 Mar;14(1):67-84.
4	FDA Approved Drug Products: Prialt (ziconotide) solution
5	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
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.
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12	Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
13	Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
14	The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
15	Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
16	Synthesis and SAR of novel 2-arylthiazolidinones as selective analgesic N-type calcium channel blockers. Bioorg Med Chem Lett. 2007 Feb 1;17(3):662-7.
17	In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6.
18	N- and L-type calcium channel antagonist improves glomerular dynamics, reverses severe nephrosclerosis, and inhibits apoptosis and proliferation in an l-NAME/SHR model. J Hypertens. 2002 May;20(5):993-1000.
19	Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
20	Clinical pipeline report, company report or official report of Convergence Pharmaceuticals Ltd.
21	N,N-dialkyl-dipeptidylamines as novel N-type calcium channel blockers. Bioorg Med Chem Lett. 1999 Mar 22;9(6):907-12.
22	CNSB004 (Leconotide) causes antihyperalgesia without side effects when given intravenously: a comparison with ziconotide in a rat model of diabetic neuropathic pain. Pain Med. 2010 Feb;11(2):262-73.
23	Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008159)
24	Synthesis and biological activity of substituted bis-(4-hydroxyphenyl)methanes as N-type calcium channel blockers. Bioorg Med Chem Lett. 1999 Aug 16;9(16):2447-52.
25	US patent application no. 2012,0172,429, Permanently charged sodium and calcium channel blockers as anti- inflammatory agents.
26	Cerner Multum, Inc. "Australian Product Information.".
27	Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.