Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMSLJP4)

• Drug Name: Ziconotide Drug Info
• 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
• Cross-matching ID:
  PubChem CID: 16135415
  ChEBI ID: CHEBI:135912
  CAS Number: CAS 107452-89-1
  TTD Drug ID: DMSLJP4
  INTEDE Drug ID: DR1728

Molecule-Related Drug Atlas

Drug(s) Targeting Voltage-gated calcium channel alpha Cav2.2 (CACNA1B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LOMERIZINE	DME0TC8	Migraine	8A80	Approved	[5]
Hesperidin	DMI5DW1	Vascular purpura	3B60	Approved	[6]
Cilnidipine	DM1975O	High blood pressure	BA00	Phase 3	[7]
Ralfinamide	DMUNMY0	Neuropathic pain	8E43.0	Phase 3	[8]
CNV-2197944	DMLT7JV	Pain	MG30-MG3Z	Phase 2	[9]
Ritanserin	DM0X36Y	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 3	[10]
CNSB-004	DMHAI0M	Pain	MG30-MG3Z	Preclinical	[11]
TH-9229	DMG1MPD	Reperfusion injury	ND56.Z	Terminated	[12]
PD-157667	DM61NFD	N. A.	N. A.	Terminated	[13]
PD-0204318	DMGKVPH	Pain	MG30-MG3Z	Terminated	[14]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[15]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[16]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[17]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[18]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[19]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[20]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[21]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[22]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[16]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[23]

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]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[4]

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] Emerging treatments for traumatic brain injury. Expert Opin Emerg Drugs. 2009 Mar;14(1):67-84.
• [4] Integrated analysis on the physicochemical properties of dihydropyridine calcium channel blockers in grapefruit juice interactions. Curr Pharm Biotechnol. 2012 Jul;13(9):1705-17.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
• [9] Clinical pipeline report, company report or official report of Convergence Pharmaceuticals Ltd.
• [10] N,N-dialkyl-dipeptidylamines as novel N-type calcium channel blockers. Bioorg Med Chem Lett. 1999 Mar 22;9(6):907-12.
• [11] 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.
• [12] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008159)
• [13] 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.
• [14] US patent application no. 2012,0172,429, Permanently charged sodium and calcium channel blockers as anti- inflammatory agents.
• [15] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [16] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [17] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [18] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [19] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [20] 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.
• [21] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [22] 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.
• [23] 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.