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

General Information of Drug (ID: DM983QP)

• Drug Name: CV-4093 Drug Info
• Synonyms: Manidipine dihydrochloride; 89226-75-5; Manidipine 2HCl; manidipine hydrochloride; Calslot; Franidipine hydrochloride; Manidipine.2HCl; Manidipine (dihydrochloride); (+-)-Manidipine hydrochloride; 3-(2-(4-Benzhydrylpiperazin-1-yl)ethyl) 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate dihydrochloride; DSSTox_CID_796; DSSTox_RID_75794; DSSTox_GSID_20796; 3-(2-(4-Benzhydrylpiperazin-1-yl)ethyl) 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 150762
  ChEBI ID: CHEBI:31800
  CAS Number: CAS 89226-75-5
  TTD Drug ID: DM983QP
  INTEDE Drug ID: DR1002

Molecule-Related Drug Atlas

Drug(s) Targeting Voltage-gated calcium channel alpha Cav1.3 (CACNA1D)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ARC029	DMYNJHI	Alzheimer disease	8A20	Phase 3	[1]
SIPATRIGINE	DMMQ4GC	Neurological disorder	6B60	Discontinued in Phase 2	[3]
SNAP-5089	DMROJEN	Heart arrhythmia	BC65	Terminated	[4]
TH-9229	DMG1MPD	Reperfusion injury	ND56.Z	Terminated	[5]
CGS-27830	DM8TLY3	N. A.	N. A.	Terminated	[6]
PD-32577	DMBA15J	Discovery agent	N.A.	Investigative	[7]
CPU-228	DMM8FUT	Cardiac failure	BD10-BD13	Investigative	[8]
(-)-(S)-BayK8644	DMEA9KH	Discovery agent	N.A.	Investigative	[8]
[3H](+)-isradipine	DM7QE1J	Discovery agent	N.A.	Investigative	[9]
MEBUDIPINE	DM0P59E	Discovery agent	N.A.	Investigative	[10]

Drug(s) Targeting Voltage-gated calcium channel alpha Cav1.2 (CACNA1C)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RAUWOLFIA SERPENTINA ROOT	DMWTVAN	Discovery agent	N.A.	Approved	[11]
ARC029	DMYNJHI	Alzheimer disease	8A20	Phase 3	[1]
SNAP-5089	DMROJEN	Heart arrhythmia	BC65	Terminated	[12]
NIGULDIPINE	DMSPWMF	N. A.	N. A.	Terminated	[11]
TH-9229	DMG1MPD	Reperfusion injury	ND56.Z	Terminated	[5]
CGS-27830	DM8TLY3	N. A.	N. A.	Terminated	[6]
R-56865	DMYTI3J	Angina pectoris	BA40	Terminated	[13]
PD-32577	DMBA15J	Discovery agent	N.A.	Investigative	[7]
CPU-228	DMM8FUT	Cardiac failure	BD10-BD13	Investigative	[14]
(-)-(S)-BayK8644	DMEA9KH	Discovery agent	N.A.	Investigative	[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 Cav1.2 (CACNA1C)	TTZIFHC	CAC1C_HUMAN	Inhibitor	[1]
Voltage-gated calcium channel alpha Cav1.3 (CACNA1D)	TT7RGTM	CAC1D_HUMAN	Inhibitor	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[2]

References

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• [2] Effect of grapefruit juice on the disposition of manidipine enantiomers in healthy subjects. Br J Clin Pharmacol. 2006 May;61(5):533-7.
• [3] Synthesis and characterization of N-(acenaphth-5-yl)-N'-(4-methoxynaphth-1-yl)guanidine as a glutamate release inhibitor and potential anti-ischemic agent, Bioorg. Med. Chem. Lett. 5(19):2259-2262 (1995).
• [4] Discovery of alpha 1a-adrenergic receptor antagonists based on the L-type Ca2+ channel antagonist niguldipine. J Med Chem. 1995 May 12;38(10):1579-81.
• [5] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008159)
• [6] CGS 27830, a potent nonpeptide endothelin receptor antagonist, Bioorg. Med. Chem. Lett. 3(10):2099-2104 (1993).
• [7] 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.
• [8] 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. (Target id: 530).
• [9] alpha 1D (Cav1.3) subunits can form l-type Ca2+ channels activating at negative voltages. J Biol Chem. 2001 Jun 22;276(25):22100-6.
• [10] Antagonism of 4-substituted 1,4-dihydropyridine-3,5-dicarboxylates toward voltage-dependent L-type Ca2+ channels Ca V 1.3 and Ca V 1.2. Bioorg Med Chem. 2010 May 1;18(9):3147-58.
• [11] Alpha- and beta-adrenoceptors: from the gene to the clinic. 2. Structure-activity relationships and therapeutic applications. J Med Chem. 1995 Sep 15;38(19):3681-716.
• [12] Design and synthesis of novel dihydropyridine alpha-1a antagonists. Bioorg Med Chem Lett. 1999 Oct 4;9(19):2843-8.
• [13] Novel calcium antagonists with both calcium overload inhibition and antioxidant activity. 1. 2-(3, 5-di-tert-butyl-4-hydroxyphenyl)-3-(aminopropyl)... J Med Chem. 1998 Oct 22;41(22):4309-16.
• [14] 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. (Target id: 529).
• [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.