Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTFK1JQ)

• DTT Name: Voltage-gated calcium channel alpha-2/delta-1 (CACNA2D1)
• Synonyms: Voltage-gated calcium channel subunit alpha-2/delta-1; Voltage-dependent calcium channel subunit delta-1; Voltage-dependent calcium channel subunit alpha-2-1; MHS3; CCHL2A; CACNL2A; CACNA2D1
• Gene Name: CACNA2D1
• DTT Type: Successful target; [1]
• BioChemical Class: Voltage-gated ion channel
• UniProt ID: CA2D1_HUMAN
• TTD ID: T84316
• Sequence:
  MAAGCLLALTLTLFQSLLIGPSSEEPFPSAVTIKSWVDKMQEDLVTLAKTASGVNQLVDI
  YEKYQDLYTVEPNNARQLVEIAARDIEKLLSNRSKALVRLALEAEKVQAAHQWREDFASN
  EVVYYNAKDDLDPEKNDSEPGSQRIKPVFIEDANFGRQISYQHAAVHIPTDIYEGSTIVL
  NELNWTSALDEVFKKNREEDPSLLWQVFGSATGLARYYPASPWVDNSRTPNKIDLYDVRR
  RPWYIQGAASPKDMLILVDVSGSVSGLTLKLIRTSVSEMLETLSDDDFVNVASFNSNAQD
  VSCFQHLVQANVRNKKVLKDAVNNITAKGITDYKKGFSFAFEQLLNYNVSRANCNKIIML
  FTDGGEERAQEIFNKYNKDKKVRVFTFSVGQHNYDRGPIQWMACENKGYYYEIPSIGAIR
  INTQEYLDVLGRPMVLAGDKAKQVQWTNVYLDALELGLVITGTLPVFNITGQFENKTNLK
  NQLILGVMGVDVSLEDIKRLTPRFTLCPNGYYFAIDPNGYVLLHPNLQPKPIGVGIPTIN
  LRKRRPNIQNPKSQEPVTLDFLDAELENDIKVEIRNKMIDGESGEKTFRTLVKSQDERYI
  DKGNRTYTWTPVNGTDYSLALVLPTYSFYYIKAKLEETITQARYSETLKPDNFEESGYTF
  IAPRDYCNDLKISDNNTEFLLNFNEFIDRKTPNNPSCNADLINRVLLDAGFTNELVQNYW
  SKQKNIKGVKARFVVTDGGITRVYPKEAGENWQENPETYEDSFYKRSLDNDNYVFTAPYF
  NKSGPGAYESGIMVSKAVEIYIQGKLLKPAVVGIKIDVNSWIENFTKTSIRDPCAGPVCD
  CKRNSDVMDCVILDDGGFLLMANHDDYTNQIGRFFGEIDPSLMRHLVNISVYAFNKSYDY
  QSVCEPGAAPKQGAGHRSAYVPSVADILQIGWWATAAAWSILQQFLLSLTFPRLLEAVEM
  EDDDFTASLSKQSCITEQTQYFFDNDSKSFSGVLDCGNCSRIFHGEKLMNTNLIFIMVES
  KGTCPCDTRLLIQAEQTSDGPNPCDMVKQPRYRKGPDVCFDNNVLEDYTDCGGVSGLNPS
  LWYIIGIQFLLLWLVSGSTHRLL
• Function: The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Plays an important role in excitation-contraction coupling.
• KEGG Pathway:
  MAPK signaling pathway (hsa04010)
  Cardiac muscle contraction (hsa04260)
  Adrenergic signaling in cardiomyocytes (hsa04261)
  Oxytocin signaling pathway (hsa04921)
  Hypertrophic cardiomyopathy (HCM) (hsa05410)
  Arrhythmogenic right ventricular cardiomyopathy (ARVC) (hsa05412)
  Dilated cardiomyopathy (hsa05414)

Molecular Interaction Atlas (MIA) of This DTT

6 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amlodipine	DMBDAZV	Angina pectoris	BA40	Approved	[1]
Diltiazem	DMAI7ZV	Angina pectoris	BA40	Approved	[2]
Lercanidipine	DMPWSEM	Hypertension	BA00-BA04	Approved	[3]
Nitrendipine	DM21C09	Hypertension	BA00-BA04	Approved	[4]
Pregabalin	DMDVP3B	Chronic obstructive pulmonary disease	CA22	Approved	[5]
Mirogabalin	DM5GIWZ	Peripheral neuropathy	8C0Z	Registered	[6]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Imagabalin	DMRLVUD	Generalized anxiety disorder	6B00	Phase 3	[7]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NP-118809	DM8A64W	Pain	MG30-MG3Z	Discontinued in Phase 2	[8]

54 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(R)-3-(aminomethyl)-4-(furan-2-yl)butanoic acid	DM2DVNT	Discovery agent	N.A.	Investigative	[9]
(S)-2-amino-2-cyclohexylacetic acid	DMVD05E	Discovery agent	N.A.	Investigative	[10]
(S)-2-amino-2-o-tolylacetic acid	DMG9KMN	Discovery agent	N.A.	Investigative	[10]
(S)-2-amino-2-p-tolylacetic acid	DMCDZ8A	Discovery agent	N.A.	Investigative	[10]
(S)-2-amino-2-phenylpropanoic acid	DM2104G	Discovery agent	N.A.	Investigative	[10]
(S)-2-amino-3-(benzylthio)propanoic acid	DM6OUW0	Discovery agent	N.A.	Investigative	[10]
(S)-2-amino-3-cyclohexylpropanoic acid	DM1GBX8	Discovery agent	N.A.	Investigative	[10]
(S)-2-amino-4-(benzylthio)butanoic acid	DMF8I2W	Discovery agent	N.A.	Investigative	[10]
(S)-3-(aminomethyl)-4-(furan-2-yl)butanoic acid	DMTBG57	Discovery agent	N.A.	Investigative	[9]
(S)-phenylglycine	DMAI1HU	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-(3,3-diphenylpropyl)piperazine	DMTYKMR	Discovery agent	N.A.	Investigative	[8]
1-benzhydryl-4-(4,4-diphenylbutyl)piperazine	DM5SWL7	Discovery agent	N.A.	Investigative	[8]
2-(1-(aminomethyl)-3-butylcyclopentyl)acetic acid	DMFXDY3	Discovery agent	N.A.	Investigative	[11]
2-(1-(aminomethyl)-3-ethylcyclopentyl)acetic acid	DM1ASK6	Discovery agent	N.A.	Investigative	[11]
2-amino-2-(2,3-difluorophenyl)acetic acid	DMWDENZ	Discovery agent	N.A.	Investigative	[10]
2-amino-2-(2,4-difluorophenyl)acetic acid	DMSAFUK	Discovery agent	N.A.	Investigative	[10]
2-amino-2-(2-fluorophenyl)acetic acid	DMLXOHE	Discovery agent	N.A.	Investigative	[10]
2-amino-2-(3-bromophenyl)acetic acid	DMEX6AM	Discovery agent	N.A.	Investigative	[10]
2-amino-2-(3-chloro-4-fluorophenyl)acetic acid	DMMU1CQ	Discovery agent	N.A.	Investigative	[10]
2-amino-2-(3-chlorophenyl)acetic acid	DMPZX8U	Discovery agent	N.A.	Investigative	[10]
2-amino-2-(thiophen-2-yl)acetic acid	DMHQNZD	Discovery agent	N.A.	Investigative	[10]
2-amino-4-(2-methyl-benzylsulfanyl)-butyric acid	DMULSNQ	Discovery agent	N.A.	Investigative	[10]
3-(aminomethyl)-4-(furan-2-yl)butanoic acid	DM5497S	Discovery agent	N.A.	Investigative	[9]
3-(aminomethyl)-4-(furan-3-yl)butanoic acid	DMG3FPJ	Discovery agent	N.A.	Investigative	[9]
3-(aminomethyl)-4-(thiophen-2-yl)butanoic acid	DMT72FB	Discovery agent	N.A.	Investigative	[9]
3-(aminomethyl)-4-(thiophen-3-yl)butanoic acid	DMWO1Z7	Discovery agent	N.A.	Investigative	[9]
3-Aminomethyl-5-methyl-hexanoic acid	DMTYXH1	Discovery agent	N.A.	Investigative	[12]
4-(2,3-dichlorobenzylthio)-2-aminobutanoic acid	DMGOHSF	Discovery agent	N.A.	Investigative	[10]
4-(2,5-dichlorobenzylthio)-2-aminobutanoic acid	DMKVH90	Discovery agent	N.A.	Investigative	[10]
4-(2-bromobenzylthio)-2-aminobutanoic acid	DMZ9TSR	Discovery agent	N.A.	Investigative	[10]
4-(2-cyanobenzylthio)-2-aminobutanoic acid	DM82D9N	Discovery agent	N.A.	Investigative	[10]
4-(2-methoxybenzylthio)-2-aminobutanoic acid	DMNSKXR	Discovery agent	N.A.	Investigative	[10]
4-(2-nitrobenzylthio)-2-aminobutanoic acid	DMC1KEG	Discovery agent	N.A.	Investigative	[10]
4-(3,4-dichlorobenzylthio)-2-aminobutanoic acid	DMBEA23	Discovery agent	N.A.	Investigative	[10]
4-(3,4-dimethylbenzylthio)-2-aminobutanoic acid	DM5ZTXO	Discovery agent	N.A.	Investigative	[10]
4-(3,5-dichlorobenzylthio)-2-aminobutanoic acid	DMM3F9K	Discovery agent	N.A.	Investigative	[10]
4-(3,5-dimethylbenzylthio)-2-aminobutanoic acid	DM9MIQB	Discovery agent	N.A.	Investigative	[10]
4-(3-bromobenzylthio)-2-aminobutanoic acid	DML3VB7	Discovery agent	N.A.	Investigative	[10]
4-(3-chlorobenzylthio)-2-aminobutanoic acid	DMQVXMZ	Discovery agent	N.A.	Investigative	[10]
4-(3-cyanobenzylthio)-2-aminobutanoic acid	DMSUB8D	Discovery agent	N.A.	Investigative	[10]
4-(3-fluorobenzylthio)-2-aminobutanoic acid	DMXLC94	Discovery agent	N.A.	Investigative	[10]
4-(3-methoxybenzylthio)-2-aminobutanoic acid	DMTPL0C	Discovery agent	N.A.	Investigative	[10]
4-(3-nitrobenzylthio)-2-aminobutanoic acid	DM4WI0Y	Discovery agent	N.A.	Investigative	[10]
4-(4-bromobenzylthio)-2-aminobutanoic acid	DMHWIMO	Discovery agent	N.A.	Investigative	[10]
4-(4-chlorobenzylthio)-2-aminobutanoic acid	DMENLUP	Discovery agent	N.A.	Investigative	[10]
4-(4-tert-butylbenzylthio)-2-aminobutanoic acid	DMG6DV9	Discovery agent	N.A.	Investigative	[10]
ETHIONINE	DMGESUH	Discovery agent	N.A.	Investigative	[10]
Gababutin	DMDEAWS	Discovery agent	N.A.	Investigative	[11]
N'-Acridin-9-yl-N,N-diethyl-butane-1,4-diamine	DM1XH8D	Discovery agent	N.A.	Investigative	[13]
N,4-dibenzhydrylpiperazine-1-carboxamide	DMOG37L	Discovery agent	N.A.	Investigative	[8]
PD-144550	DM03526	Discovery agent	N.A.	Investigative	[12]
Rac-2-amino-4-phenylbutanoic acid	DMTUR6C	Discovery agent	N.A.	Investigative	[10]
Rac-2-amino-5-cyclohexylpentanoic acid	DMU0746	Discovery agent	N.A.	Investigative	[10]
Trans-dimethyl gababutin	DM8E9YS	Discovery agent	N.A.	Investigative	[14]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Chronic obstructive pulmonary disease	CA23	Lung tissue	9.36E-01	-0.03	-0.13
Chronic obstructive pulmonary disease	CA23	Small airway epithelium	2.81E-05	-0.15	-0.68

References

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• [14] Synthesis and in vivo evaluation of bicyclic gababutins. Bioorg Med Chem Lett. 2010 Jan 15;20(2):461-4.