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

General Information of Drug (ID: DMV6EMN)

• Drug Name: (-)-(R)-efonidipine Drug Info
• Synonyms: UNII-BF2E1WS195; BF2E1WS195; ()-2-[benzyl (phenyl) amino] ethyl 1,4-dihydro-2,6- dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-3-pyridinecarboxylate hydrochloride ethano; Efonidipine, (-)-; (-)-(R)-efonidipine; (R)-(-)-Efonidipine; 128194-13-8; Efonidipine (R)-form [MI]; GTPL2519; ZINC38139973; 3-Pyridinecarboxylic acid, 5-(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-, 2-(phenyl(phenylmethyl)amino)ethyl ester, (4R)-

Indication

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

• Cross-matching ID:
  PubChem CID: 9830707
  ChEBI ID: CHEBI:146219
  CAS Number: CAS 128194-13-8
  TTD Drug ID: DMV6EMN

Molecule-Related Drug Atlas

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	[3]
ARC029	DMYNJHI	Alzheimer disease	8A20	Phase 3	[4]
SNAP-5089	DMROJEN	Heart arrhythmia	BC65	Terminated	[5]
NIGULDIPINE	DMSPWMF	N. A.	N. A.	Terminated	[3]
TH-9229	DMG1MPD	Reperfusion injury	ND56.Z	Terminated	[6]
CGS-27830	DM8TLY3	N. A.	N. A.	Terminated	[7]
R-56865	DMYTI3J	Angina pectoris	BA40	Terminated	[8]
PD-32577	DMBA15J	Discovery agent	N.A.	Investigative	[9]
CPU-228	DMM8FUT	Cardiac failure	BD10-BD13	Investigative	[10]
(-)-(S)-BayK8644	DMEA9KH	Discovery agent	N.A.	Investigative	[10]

Drug(s) Targeting Voltage-gated calcium channel alpha Cav3.1 (CACNA1G)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[11]
Ethosuximide	DMDZ9LT	Epilepsy	8A60-8A68	Approved	[12]
Trimethadione	DM0Q8MZ	Absence epilepsy		Approved	[13]
Paramethadione	DMR5ZUP	Absence epilepsy		Approved	[13]
Methsuximide	DM6L5VO	Absence epilepsy		Approved	[14]
Penfluridol	DMG1DTE	Schizophrenia	6A20	Approved	[15]
PD-200390	DMPW28M	Insomnia	7A00-7A0Z	Phase 2	[16]
NGD 94-1	DMM1Y8F	Schizophrenia	6A20	Phase 1	[15]
ML218	DM3D21X	Discovery agent	N.A.	Investigative	[17]
KYS-05001	DM3MID9	Discovery agent	N.A.	Investigative	[18]

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	Blocker (channel blocker)	[2]
Voltage-gated calcium channel alpha Cav3.1 (CACNA1G)	TT729IR	CAC1G_HUMAN	Blocker (channel blocker)	[2]

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: 2519).
• [2] Identification of R(-)-isomer of efonidipine as a selective blocker of T-type Ca2+ channels. Br J Pharmacol. 2004 Dec;143(8):1050-7.
• [3] 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.
• [4] Dihydropyrimidines: novel calcium antagonists with potent and long-lasting vasodilative and antihypertensive activity. J Med Chem. 1989 Oct;32(10):2399-406.
• [5] Design and synthesis of novel dihydropyridine alpha-1a antagonists. Bioorg Med Chem Lett. 1999 Oct 4;9(19):2843-8.
• [6] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008159)
• [7] CGS 27830, a potent nonpeptide endothelin receptor antagonist, Bioorg. Med. Chem. Lett. 3(10):2099-2104 (1993).
• [8] 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.
• [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] 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).
• [11] Mechanism of tissue-selective drug action in the cardiovascular system. Mol Interv. 2005 Apr;5(2):84-93.
• [12] Maladaptive homeostatic plasticity in a rodent model of central pain syndrome: thalamic hyperexcitability after spinothalamic tract lesions. J Neurosci. 2008 Nov 12;28(46):11959-69.
• [13] Prophylactic and therapeutic functions of T-type calcium blockers against noise-induced hearing loss. Hear Res. 2007 Apr;226(1-2):52-60.
• [14] Block of cloned human T-type calcium channels by succinimide antiepileptic drugs. Mol Pharmacol. 2001 Nov;60(5):1121-32.
• [15] Differential inhibition of T-type calcium channels by neuroleptics. J Neurosci. 2002 Jan 15;22(2):396-403.
• [16] Pfizer. Product Development Pipeline. March 31 2009.
• [17] The Discovery and Characterization of ML218: A Novel, Centrally Active T-Type Calcium Channel Inhibitor with Robust Effects in STN Neurons and in a Rodent Model of Parkinson's Disease. ACS Chem Neurosci. 2011 Dec 21;2(12):730-742.
• [18] Discovery of potent T-type calcium channel blocker. Bioorg Med Chem Lett. 2007 Nov 1;17(21):5740-3.