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

General Information of Drug (ID: DMPWSEM)

• Drug Name: Lercanidipine Drug Info
• Synonyms: Lercanil; Masnidipine; Lercanidipine [INN]; Lercanidipine (INN); Lercanil (TN); REC 15-2375; Zanidip (TN); REC-15-2375; Methyl-1,1-dimethyl-2-(N-(3,3-diphenylpropyl)-N-methylamino)ethyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate; (+-)-2-((3,3-Diphenylpropyl)methylamino)-1,1-dimethylethyl methyl1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridinedicarboxylate; 1-[(3,3-diphenylpropyl)(methyl)amino]-2-methylpropan-2-yl methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate; 3,5-Pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-, 3-[2-[(3,3-diphenylpropyl)methylamino]-1,1-dimethylethyl] 5-methyl ester; 5-O-[1-[3,3-diphenylpropyl(methyl)amino]-2-methylpropan-2-yl] 3-O-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

Indication

Disease Entry	ICD 11	Status	REF
Hypertension	BA00-BA04	Approved	[1]

• Therapeutic Class: Antihypertensive Agents
• Cross-matching ID:
  PubChem CID: 65866
  ChEBI ID: CHEBI:135930
  CAS Number: CAS 100427-26-7
  TTD Drug ID: DMPWSEM
  INTEDE Drug ID: DR0924

Molecule-Related Drug Atlas

Drug(s) Targeting Voltage-gated calcium channel alpha-2/delta-1 (CACNA2D1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Diltiazem	DMAI7ZV	Angina pectoris	BA40	Approved	[5]
Nitrendipine	DM21C09	Hypertension	BA00-BA04	Approved	[6]
Pregabalin	DMDVP3B	Chronic obstructive pulmonary disease	CA22	Approved	[7]
Amlodipine	DMBDAZV	Angina pectoris	BA40	Approved	[8]
Mirogabalin	DM5GIWZ	Peripheral neuropathy	8C0Z	Registered	[9]
Imagabalin	DMRLVUD	Generalized anxiety disorder	6B00	Phase 3	[10]
NP-118809	DM8A64W	Pain	MG30-MG3Z	Discontinued in Phase 2	[11]
PD-144550	DM03526	Discovery agent	N.A.	Investigative	[12]
3-Aminomethyl-5-methyl-hexanoic acid	DMTYXH1	Discovery agent	N.A.	Investigative	[12]
(S)-2-amino-3-cyclohexylpropanoic acid	DM1GBX8	Discovery agent	N.A.	Investigative	[13]

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	[14]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[15]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[16]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[20]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[21]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[15]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[22]

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	[23]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[24]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[25]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[4]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[26]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[27]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[28]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[29]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[30]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[4]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[31]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[4]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[4]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[4]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[32]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[33]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[4]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[4]
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[4]
Metronidazole	DMTIVEN	Abscess		Approved	[34]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Voltage-gated calcium channel alpha-2/delta-1 (CACNA2D1)	TTFK1JQ	CA2D1_HUMAN	Blocker	[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	[4]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Substrate	[4]

References

• [1] Fixed-dose combination lercanidipine/enalapril. Drugs. 2007;67(1):95-106; discussion 107-8.
• [2] Treatment of essential hypertension with calcium channel blockers: what is the place of lercanidipine Expert Opin Drug Metab Toxicol. 2009 Aug;5(8):981-7.
• [3] Lercanidipine in hypertension. Vasc Health Risk Manag. 2005;1(3):173-82.
• [4] Drug Interactions Flockhart Table
• [5] Egr-1, the potential target of calcium channel blockers in cardioprotection with ischemia/reperfusion injury in rats. Cell Physiol Biochem. 2009;24(1-2):17-24.
• [6] Sulfobutyl ether-alkyl ether mixed cyclodextrin derivatives with enhanced inclusion ability. J Pharm Sci. 2009 Dec;98(12):4769-80.
• [7] Pregabalin reduces the release of synaptic vesicles from cultured hippocampal neurons. Mol Pharmacol. 2006 Aug;70(2):467-76.
• [8] A first drug combination for the treatment of arterial hypertension with a calcium channel antagonist (amlodipine besylate) and an angiotensin receptor blocker (valsartan): Exforge. Rev Med Liege. 2007 Nov;62(11):688-94.
• [9] Efficacy and safety of mirogabalin (DS-5565) for the treatment of diabetic peripheral neuropathic pain: a randomized, double-blind, placebo- and active comparator-controlled, adaptive proof-of-concept phase 2 study. Diabetes Care. 2014 Dec;37(12):3253-61.
• [10] Methodology for rapid measures of glutamate release in rat brain slices using ceramic-based microelectrode arrays: basic characterization and drug pharmacology. Brain Res. 2011 Jul 15;1401:1-9.
• [11] Scaffold-based design and synthesis of potent N-type calcium channel blockers. Bioorg Med Chem Lett. 2009 Nov 15;19(22):6467-72.
• [12] Enantioselective synthesis of PD144723: a potent stereospecific anticonvulsant, Bioorg. Med. Chem. Lett. 4(6):823-826 (1994).
• [13] Structure-activity relationships of alpha-amino acid ligands for the alpha2delta subunit of voltage-gated calcium channels. Bioorg Med Chem Lett. 2006 Mar 1;16(5):1138-41.
• [14] 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.
• [15] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [16] 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.
• [17] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [18] 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.
• [19] 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.
• [20] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [21] 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.
• [22] 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.
• [23] 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.
• [24] 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.
• [25] 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.
• [26] 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.
• [27] Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
• [28] Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
• [29] Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000.
• [30] Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.
• [31] 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.
• [32] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [33] Prediction of cytochrome P450 3A inhibition by verapamil enantiomers and their metabolites. Drug Metab Dispos. 2004 Feb;32(2):259-66.
• [34] 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.