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

General Information of Drug (ID: DM0ZOGX)

• Drug Name: Linopirdine Drug Info
• Synonyms: AVIVA; Linopirine; DuP-996

Indication

Disease Entry	ICD 11	Status	REF
Cognitive impairment	6D71	Phase 3	[1]

• Cross-matching ID:
  PubChem CID: 3932
  ChEBI ID: CHEBI:34823
  CAS Number: CAS 105431-72-9
  TTD Drug ID: DM0ZOGX
  INTEDE Drug ID: DR0958

Molecule-Related Drug Atlas

Drug(s) Targeting Voltage-gated potassium channel Kv7.3 (KCNQ3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Retigabine	DMGNYIH	Behcet disease	4A62	Approved	[4]
ICA-105665	DMP925B	Epilepsy	8A60-8A68	Phase 2	[5]
XEN1101	DMJVL57	Epilepsy	8A60-8A68	Phase 1	[6]
ICA-69673	DM1RZVI	Pain	MG30-MG3Z	Preclinical	[7]
[14C]TEA	DM6SFYH	Discovery agent	N.A.	Investigative	[8]
PD-32577	DMBA15J	Discovery agent	N.A.	Investigative	[9]

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	[10]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[11]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[12]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[13]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[14]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[15]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[16]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[17]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[11]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[18]

Drug(s) Metabolized By Cytochrome P450 3A5 (CYP3A5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[19]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[20]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[21]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[22]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[23]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[24]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[25]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[26]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[27]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[22]

Drug(s) Metabolized By Cytochrome P450 3A7 (CYP3A7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[28]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[22]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[22]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[22]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[29]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[30]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[22]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[22]
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[22]
Metronidazole	DMTIVEN	Abscess		Approved	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Voltage-gated potassium channel Kv7.3 (KCNQ3)	TTIVDM3	KCNQ3_HUMAN	Modulator	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[3]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[3]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Substrate	[3]

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: 2599).
• [2] The M-channel blocker linopirdine is an agonist of the capsaicin receptor TRPV1. J Pharmacol Sci. 2010;114(3):332-40.
• [3] Induction of cytochromes P-450 2B and 3A in mice following the dietary administration of the novel cognitive enhancer linopirdine. Drug Metab Dispos. 1994 Jan-Feb;22(1):65-73.
• [4] The urinary safety profile and secondary renal effects of retigabine (ezogabine): a first-in-class antiepileptic drug that targets KCNQ (K(v)7) potassium channels. Epilepsia. 2012 Apr;53(4):606-12.
• [5] New molecular targets for antiepileptic drugs: alpha(2)delta, SV2A, and K(v)7/KCNQ/M potassium channels. Curr Neurol Neurosci Rep. 2008 Jul;8(4):345-52.
• [6] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [7] Voltage-gated Potassium Channels as Therapeutic Drug Targets
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• [9] 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.
• [10] 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.
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• [12] 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.
• [13] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [14] 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.
• [15] 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.
• [16] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [17] 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.
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• [19] Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer. J Urol. 2008 Dec;180(6):2389-95.
• [20] Human prostate CYP3A5: identification of a unique 5'-untranslated sequence and characterization of purified recombinant protein. Biochem Biophys Res Commun. 1999 Jul 14;260(3):676-81.
• [21] Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett. 2005 Jan 10;217(1):61-72.
• [22] Drug Interactions Flockhart Table
• [23] Induction of hepatic CYP2E1 by a subtoxic dose of acetaminophen in rats: increase in dichloromethane metabolism and carboxyhemoglobin elevation. Drug Metab Dispos. 2007 Oct;35(10):1754-8.
• [24] Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
• [25] Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
• [26] Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000.
• [27] Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.
• [28] The role of cytochrome P450 3A (CYP3A) isoform(s) in oxidative metabolism of testosterone and benzphetamine in human adult and fetal liver. J Steroid Biochem Mol Biol. 1993 Jan;44(1):61-7.
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• [30] Prediction of cytochrome P450 3A inhibition by verapamil enantiomers and their metabolites. Drug Metab Dispos. 2004 Feb;32(2):259-66.
• [31] The role of human cytochrome P450 enzymes in the formation of 2-hydroxymetronidazole: CYP2A6 is the high affinity (low Km) catalyst. Drug Metab Dispos. 2013 Sep;41(9):1686-94.