Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT5HONZ)

• DTT Name: Calcium channel unspecific (CaC)
• Gene Name: CaC
• DTT Type: Successful target; [1]
• UniProt ID: NOUNIPROTAC
• TTD ID: T45993

Molecular Interaction Atlas (MIA) of This DTT

7 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bepridil	DM0RKS4	Chronic/stable angina	BA40.1	Approved	[2]
Clevidipine butyrate	DMW4M97	Hypertension	BA00-BA04	Approved	[3]
Felodipine	DMOSW35	Hypertension	BA00-BA04	Approved	[4]
Isradipine	DMA5XGH	Hypertension	BA00-BA04	Approved	[2]
Nicardipine	DMCDYW7	High blood pressure	BA00	Approved	[5]
Nimodipine	DMQ0RKZ	Cerebral vasospasm	BA85.Z	Approved	[1]
Nisoldipine	DM7ISKJ	Hypertension	BA00-BA04	Approved	[6]

11 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DIPROTEVERINE HYDROCHLORIDE	DMG8U6M	Angina pectoris	BA40	Phase 3	[7]
Arverapamil	DML27AE	Irritable bowel syndrome	DD91.0	Phase 2	[8]
ATI-2042	DMWP59B	Atrial fibrillation	BC81.3	Phase 2	[9]
HBI-3000	DM74ZKN	Heart arrhythmia	BC65	Phase 2	[10]
Nexopamil	DML5S71	Hypertension	BA00-BA04	Phase 2	[11]
S-2150	DMTAX8B	Angina pectoris	BA40	Phase 2	[12]
CM2489	DMMC6YR	Psoriasis vulgaris	EA90	Phase 1	[13]
DSP-0565	DMY95MZ	Epilepsy	8A60-8A68	Phase 1	[14]
Elpetrigine	DMIV04R	Bipolar disorder	6A60	Phase 1	[15]
Tetrandrine	DMAOJBX	Sarcoma	2A60-2C35	Phase 1	[16]
YM-16151-4	DMNLY9R	Hypertension	BA00-BA04	Phase 1	[17]

53 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AE-0047	DMTF9YV	Hypertension	BA00-BA04	Discontinued in Preregistration	[18]
Monatepil maleate	DM9ADLQ	Angina pectoris	BA40	Discontinued in Preregistration	[19]
Palonidipine hydrochloride	DMUH0KO	Hypertension	BA00-BA04	Discontinued in Preregistration	[20]
Semotiadil	DMYBPJ1	Hypertension	BA00-BA04	Discontinued in Preregistration	[21]
Anipamil	DMNEM2C	Hypertension	BA00-BA04	Discontinued in Phase 3	[22]
ELGODIPINE HYDROCHLORIDE	DMJOM31	Angina pectoris	BA40	Discontinued in Phase 3	[23]
S-12968	DMPUED3	Hypertension	BA00-BA04	Discontinued in Phase 3	[24]
AM336	DMF8KH7	Pain	MG30-MG3Z	Discontinued in Phase 2	[25]
BRL-32872A	DMRKBIU	Cardiac arrhythmias	BC9Z	Discontinued in Phase 2	[26]
CD-349	DM9P7Z2	Hypertension	BA00-BA04	Discontinued in Phase 2	[27]
Dopropidil	DMMC6H7	Angina pectoris	BA40	Discontinued in Phase 2	[28]
FLOSATIDIL	DMOCMXH	Angina pectoris	BA40	Discontinued in Phase 2	[29]
Levosemotiadil	DMKSY2R	Cardiac arrhythmias	BC9Z	Discontinued in Phase 2	[30]
Lifarizine	DM3R8TI	Nerve injury	ND56.4	Discontinued in Phase 2	[31]
S-312-d	DMQ2RDZ	Epilepsy	8A60-8A68	Discontinued in Phase 2	[32]
TAMOLARIZINE HYDROCHLORIDE	DM1L5UX	Cognitive impairment	6D71	Discontinued in Phase 2	[33]
CEREBROCRAST	DMK93VQ	Nerve injury	ND56.4	Discontinued in Phase 1	[34]
CERM-11956	DMQKRWO	Angina pectoris	BA40	Discontinued in Phase 1	[35]
IGANIDIPINE HYDROCHLORIDE	DMP8MBW	Glaucoma/ocular hypertension	9C61	Discontinued in Phase 1	[36]
KT-362	DM74BK8	Heart arrhythmia	BC65	Discontinued in Phase 1	[37]
NP-252	DMT8IGE	Hypertension	BA00-BA04	Discontinued in Phase 1	[38]
SM-6586	DM6CLX9	Hypertension	BA00-BA04	Discontinued in Phase 1	[39]
SR-33805	DM471IG	Angina pectoris	BA40	Discontinued in Phase 1	[40]
AHR-16303B	DMJZ48W	Hypertension	BA00-BA04	Terminated	[42]
AHR-16462B	DMJ6BEO	Hypertension	BA00-BA04	Terminated	[43]
AJ-3941	DMOJTZV	Cerebrovascular ischaemia	8B1Z	Terminated	[44]
CD-832	DM5FEBQ	Angina pectoris	BA40	Terminated	[45]
Clentiazem	DM8TQC9	Angina pectoris	BA40	Terminated	[46]
Darodipine	DM160FM	Cerebrovascular ischaemia	8B1Z	Terminated	[47]
DHP-218	DM5VFR0	Hypertension	BA00-BA04	Terminated	[48]
E-2050	DMQKEHA	Cerebrovascular ischaemia	8B1Z	Terminated	[49]
Emopamil	DMW210B	Cerebrovascular ischaemia	8B1Z	Terminated	[50]
LAS-30538	DM07S4N	Hyperinsulinemia	5A4Y	Terminated	[51]
Naltiazem hydrochloride	DM7T2FO	Angina pectoris	BA40	Terminated	[52]
NNC-09-0026	DMGEHZ9	Cerebrovascular ischaemia	8B1Z	Terminated	[53]
NS-638	DMPT74G	Cerebrovascular ischaemia	8B1Z	Terminated	[54]
NS-649	DMXKMRV	Alzheimer disease	8A20	Terminated	[55]
NS-696	DMI46T3	Epilepsy	8A60-8A68	Terminated	[56]
Pranidipine	DMI2N9H	Angina pectoris	BA40	Terminated	[57]
RS-93522	DMZHS9U	Hypertension	BA00-BA04	Terminated	[58]
RWJ-22108	DMBXDQG	Allergy	4A80-4A85	Terminated	[59]
RWJ-37868	DM17WNG	Epilepsy	8A60-8A68	Terminated	[60]
SB-206284A	DM5ZPQJ	Cerebrovascular ischaemia	8B1Z	Terminated	[61]
SB-237376	DMBCANZ	Arrhythmia	BC9Z	Terminated	[62]
SDZ-249482	DMPZLKC	Pain	MG30-MG3Z	Terminated	[63]
SIM-6080	DMBZ7SF	Angina pectoris	BA40	Terminated	[64]
Siratiazem	DMG90YW	Angina pectoris	BA40	Terminated	[65]
SKF-96365	DMI79JN	Angina pectoris	BA40	Terminated	[66]
SQ-33351	DM083JB	Hypertension	BA00-BA04	Terminated	[67]
UK-51656	DM23YPS	Cardiovascular disease	BA00-BE2Z	Terminated	[68]
VUF-8929	DM0CWJZ	Heart failure	BD10-BD13	Terminated	[69]
Z-6568	DMQ6K8J	Hypertension	BA00-BA04	Terminated	[70]
ZM-224832	DM8V0YA	Hypertension	BA00-BA04	Terminated	[71]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Rycals	DMXM2BZ	Heart failure	BD10-BD13	Preclinical	[41]

6 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AGN-190744	DMIKDAR	Discovery agent	N.A.	Investigative	[72]
BELFOSDIL	DM0WOS6	Discovery agent	N.A.	Investigative	[73]
CD-832.HCL	DMFYWE3	Discovery agent	N.A.	Investigative	[74]
leualacin	DMV40XH	Discovery agent	N.A.	Investigative	[75]
SR-33805A	DMPO4WX	Hypertension	BA00-BA04	Investigative	[76]
TELUDIPINE HYDROCHLORIDE	DMT4NWX	Hypertension	BA00-BA04	Investigative	[77]

References

• [1] Influence of bupropion and calcium channel antagonists on the nicotine-induced memory-related response of mice in the elevated plus maze. Pharmacol Rep. 2009 Mar-Apr;61(2):236-44.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [3] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [4] Molecular pharmacology of human Cav3.2 T-type Ca2+ channels: block by antihypertensives, antiarrhythmics, and their analogs. J Pharmacol Exp Ther. 2009 Feb;328(2):621-7.
• [5] Effect of intracoronary nicardipine on cardiac enzymes after elective percutaneous coronary intervention. Clin Cardiol. 2009 Jun;32(6):315-20.
• [6] RT-PCR and pharmacological analysis of L-and T-type calcium channels in rat carotid body. Adv Exp Med Biol. 2009;648:105-12.
• [7] Prenatal toxicity studies in rats and rabbits with the calcium channel blocker diproteverine. Reprod Toxicol. 1996 Jan-Feb;10(1):43-9.
• [8] BJMP 2010;3(4):a342
• [9] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [10] Electrophysiological properties of HBI-3000: a new antiarrhythmic agent with multiple-channel blocking properties in human ventricular myocytes. J Cardiovasc Pharmacol. 2011 Jan;57(1):79-85.
• [11] Inhibition by the combined Ca2+ and 5-HT2 receptor antagonist nexopamil (LU 49938) of intracoronary thrombus formation in a canine model of arterial stenosis and intimal damage. J Cardiovasc Pharmacol. 1993 Nov;22(5):687-94.
• [12] Pharmacodynamics of S-2150, a simultaneous calcium-blocking and alpha1-inhibiting antihypertensive drug, in rats. J Pharm Pharmacol. 2000 Mar;52(3):273-80.
• [13] Molecular pharmacology of store-operated CRAC channels
• [14] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800035668)
• [15] Clinical pipeline report, company report or official report of Jazz Pharmaceuticals.
• [16] Tetrandrine: a novel calcium channel antagonist inhibits type I calcium channels in neuroblastoma cells. Neuropharmacology. 1991 Dec;30(12A):1325-31.
• [17] Antianginal effects of YM-16151-4 in various experimental angina models. J Cardiovasc Pharmacol. 1993 May;21(5):701-8.
• [18] AE0047-mediated calcium channel blocking in vascular smooth muscles. Gen Pharmacol. 1997 Sep;29(3):337-43.
• [19] Antihypertensive, antiatherosclerotic, and plasma lipid-lowering effects of monatepil, a novel calcium antagonist with alpha 1-adrenoceptor-blocking activity in experimental animals. Am J Hypertens. 1994 Oct;7(10 Pt 2):131S-40S.
• [20] Effect of palonidipine hydrochloride (TC-81), a novel calcium antagonist, on the canine coronary artery. Nihon Yakurigaku Zasshi. 1993 Jul;102(1):23-33.
• [21] Thyroid hypertrophic effect of semotiadil fumarate, a new calcium antagonist, in rats. J Toxicol Sci. 2000 May;25(2):121-30.
• [22] Effects of the novel calcium channel blocker, anipamil, on the isolated rabbit heart. Comparison with verapamil and gallopamil. Naunyn Schmiedebergs Arch Pharmacol. 1992 Sep;346(3):339-44.
• [23] The calcium channel blocker amlodipine exerts its anti-proliferative action via p21(Waf1/Cip1) gene activation. FASEB J. 2004 Oct;18(13):1516-23.
• [24] (+)-S-12967 and (-)-S-12968: 1,4-dihydropyridine stereoisomers with calcium channel agonistic and antagonistic properties in rat resistance arteries. Br J Pharmacol. 1991 Jul;103(3):1703-8.
• [25] Intravenous injection of leconotide, an omega conotoxin: synergistic antihyperalgesic effects with morphine in a rat model of bone cancer pain.Pain Med.2011 Jun;12(6):923-41.
• [26] Combined potassium and calcium channel blocking activities as a basis for antiarrhythmic efficacy with low proarrhythmic risk: experimental profile... J Pharmacol Exp Ther. 1996 Feb;276(2):637-46.
• [27] A new Ca-antagonist, CD-349, binding to the Ca-channel of rat myocardium and brain and hog coronary artery. Jpn J Pharmacol. 1988 Dec;48(4):453-62.
• [28] Effects of bepridil and CERM 4205 (ORG 30701) on the relation between cardiac cycle length and QT duration in healthy volunteers. Am J Cardiol. 1990 Sep 1;66(5):636-41.
• [29] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [30] Binding study of semotiadil and levosemotiadil with alpha(1)-acid glycoprotein using high-performance frontal analysis. Anal Biochem. 1999 Oct 1;274(1):27-33.
• [31] The effect of lifarizine (RS-87476), a novel sodium and calcium channel modulator, on ischaemic dopamine depletion in the corpus striatum of the gerbil. Br J Pharmacol. 1993 May;109(1):175-7.
• [32] Protective effects of a selective L-type voltage-sensitive calcium channel blocker, S-312-d, on neuronal cell death. Biochem Pharmacol. 2004 Mar 15;67(6):1153-65.
• [33] Reversal of multidrug resistance in human leukemia K562 by tamolarizine, a novel calcium antagonist. Jpn J Pharmacol. 2000 Mar;82(3):265-8.
• [34] The dihydropyridine analogue cerebrocrast blocks both T-type and L-type calcium currents. Can J Physiol Pharmacol. 2009 Nov;87(11):923-32.
• [35] The anti-ischaemic activity of the novel compound, CERM 11956, compared with that of bepridil and nifedipine in isolated guinea-pig hearts. Eur J Pharmacol. 1988 May 10;149(3):195-203.
• [36] Improving effects of topical administration of iganidipine, a new calcium channel blocker, on the impaired visual evoked potential after endothelin-1 injection into the vitreous body of rabbits. CurrEye Res. 2000 Feb;20(2):101-8.
• [37] Comparative cardiac effects of KT-362 and verapamil in isolated heart--correlation to calcium channel current depression. J Cardiovasc Pharmacol. 1991 Oct;18(4):594-604.
• [38] Pharmacological characteristics of NP-252, a new dihydropyridine slow Ca2+ channel blocker, in isolated rabbit vascular smooth muscle and guinea pig myocardium: vascular selectivity. Eur J Pharmacol.1991 Oct 22;203(3):337-44.
• [39] Calcium channel blocking properties of SM-6586 in rat heart and brain as assessed by radioligand binding assay. Jpn J Pharmacol. 1993 Oct;63(2):165-9.
• [40] Effects of a new class of calcium antagonists, SR33557 (fantofarone) and SR33805, on neuronal voltage-activated Ca++ channels. J Pharmacol Exp Ther. 1994 Dec;271(3):1348-52.
• [41] Fixing ryanodine receptor Ca2+ leak - a novel therapeutic strategy for contractile failure in heart and skeletal muscle. Drug Discov Today Dis Mech. 2010 SUMMER; 7(2): e151-e157.
• [42] AHR-16303B, a novel antagonist of 5-HT2 receptors and voltage-sensitive calcium channels. J Cardiovasc Pharmacol. 1991 Jan;17(1):41-53.
• [43] A pharmacological and biochemical examination of AHR-16462B, a novel calcium antagonist coronary vasodilator/antihypertensive. Drug Development Research. 01/1991; 22(3):259-271.
• [44] Prevention by the new Ca2+ channel antagonist, AJ-3941, of loss of endothelium-dependent relaxation after subarachnoid hemorrhage in rats. Eur J Pharmacol. 1996 Nov 21;315(3):297-303.
• [45] Effects of CD-832, a new calcium antagonist, on intracranial pressure in anesthetized dogs. Life Sci. 1998;62(19):PL283-8.
• [46] Coronary and cardiac sensitivity to the vasoselective benzothiazepine-like calcium antagonist, clentiazem, in experimental heart failure. Cardiovasc Drugs Ther. 1997 Mar;11(1):71-9.
• [47] Effect of cromakalim on contractions in rabbit isolated renal artery in the presence and absence of extracellular Ca2+. Br J Pharmacol. 1989 Dec;98(4):1303-11.
• [48] Effect of DHP-218, a novel dihydropyridine phosphonate, on atrioventricular nodal conductivity compared with its vascular effect in dogs. J Cardiovasc Pharmacol. 1987 Sep;10(3):274-9.
• [49] Solubility of E2050 at various pH: a case in which apparent solubility is affected by the amount of excess solid. J Pharm Sci. 2002 Jun;91(6):1445-55.
• [50] Calcium entry and 5-HT2 receptor blockade in oliguric ischaemic acute renal failure: effects of levemopamil in conscious rats. Br J Pharmacol. 1996 Mar;117(6):1348-54.
• [51] The calcium channel blocker LAS 30538, unlike nifedipine, verapamil, diltiazem or flunarizine, potently inhibits insulin secretion in-vivo in rats and dogs. J Pharm Pharmacol. 1992 Oct;44(10):851-5.
• [52] Assessment of hyperglycemia after calcium channel blocker overdoses involving diltiazem or verapamil. Crit Care Med. 2007 Sep;35(9):2071-5.
• [53] Pharmacological profile of a novel neuronal calcium channel blocker includes reduced cerebral damage and neurological deficits in rat focal ischemia. Pharmacol Biochem Behav. 1994 May;48(1):77-85.
• [54] Pharmacological profile and anti-ischemic properties of the Ca(2+)-channel blocker NS-638. Neurol Res. 1995 Oct;17(5):353-60.
• [55] Effects of Ca2+ and Na+ channel inhibitors in vitro and in global cerebral ischaemia in vivo. Eur J Pharmacol. 1997 Aug 6;332(2):121-31.
• [56] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005355)
• [57] Pranidipine, a new 1,4-dihydropyridine calcium channel blocker, enhances cyclic GMP-independent nitric oxide-induced relaxation of the rat aorta. Mol Cell Biochem. 1998 Jan;178(1-2):335-43.
• [58] Intranasal delivery of RS-93522, a dihydropyridine-type calcium-channel antagonist. Pharm Res. 1991 Jan;8(1):134-5.
• [59] Design and discovery of RWJ 22108--a novel bronchoselective calcium channel blocker. Drug Des Discov. 1998 May;15(3):135-48.
• [60] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008896)
• [61] The effects of SB 206284A, a novel neuronal calcium-channel antagonist, in models of cerebral ischemia. J Cereb Blood Flow Metab. 1997 Apr;17(4):421-9.
• [62] Electrophysiologic effects of SB-237376: a new antiarrhythmic compound with dual potassium and calcium channel blocking action. J Cardiovasc Pharmacol. 2003 Mar;41(3):414-21.
• [63] Physiology and Pharmacology of the Vanilloid Receptor. Curr Neuropharmacol. 2006 January; 4(1): 1-15.
• [64] Determination of the calcium antagonist SIM6080 and its N- and O-demethylated metabolites in plasma, urine and tissues by high-performance liquid chromatography. J Chromatogr B Biomed Appl. 1996 Feb 9;676(1):77-85.
• [65] Comparison of the effects of diltiazem and its analogue siratiazem on contractility in arteries, ileum and cardiac muscle. J Auton Pharmacol. 1995 Apr;15(2):107-13.
• [66] The transient receptor potential channel antagonist SKF96365 is a potent blocker of low-voltage-activated T-type calcium channels. Br J Pharmacol. 2010 Jul;160(6):1464-75.
• [67] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002577)
• [68] Long-acting dihydropyridine calcium antagonists. 4. Synthesis and structure-activity relationships for a series of basic and nonbasic derivatives of 2-[(2-aminoethoxy)methyl]-1,4-dihydropyridine calcium antagonists. J Med Chem. 1990 Feb;33(2):585-91.
• [69] In vitro and in vivo characterization of a calcium modulator of the diphenylalkylamine type with selective coronary dilatory properties. Arzneimittelforschung. 1997 Nov;47(11):1211-8.
• [70] Determination of the dihydropyridine aryloxypropanolamine Z6568 and its acidic metabolites in plasma, urine and tissues by solid phase extraction and liquid chromatography/negative-ion mass spectrometry. J Mass Spectrom. 1996 Sep;31(9):994-1002.
• [71] Diuretic and antihypertensive activity of ZENECA ZM224,832: a novel eukalemic diuretic with calcium channel blocking activity. Pharmacology. 1994 Mar;48(3):167-75.
• [72] The antiinflammatory activity of topically applied novel calcium-channel antagonists. Inflammation. 1995 Apr;19(2):261-75.
• [73] Determination of belfosdil, a new calcium channel blocker, in human plasma by capillary gas chromatography with nitrogen-phosphorus detection. J Chromatogr. 1990 May 18;527(2):343-50.
• [74] Actions of a new Ca2+ channel antagonist, CD832, on two types of Ca2+ channels in smooth muscle. Eur J Pharmacol. 1994 Feb 11;252(3):267-74.
• [75] Leualacin, a novel calcium blocker from Hapsidospora irregularis. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties. J Antibiot (Tokyo). 1992 Jun;45(6):899-905.
• [76] Vascular calcium overload produced by vitamin D3, in rats. Effect of treatment with SR 33805, a novel calcium entry blocker. Cardiovasc Res. 1995 Dec;30(6):1038-43.
• [77] Effects of R-enantiomer (GR66234A) and L-enantiomer (GR66235A) of telupidine, a new dihydropyridine derivative, on cell lines displaying the multidrug resistant phenotype. Haematologica. 1994 Jul-Aug;79(4):328-33.