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

General Information of Drug (ID: DM0E4OW)

• Drug Name: PD-118057 Drug Info
• Synonyms: PD118057; PD 118057

Indication

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

• Cross-matching ID:
  PubChem CID: 9864959
  CAS Number: CAS 313674-97-4
  TTD Drug ID: DM0E4OW

Molecule-Related Drug Atlas

Drug(s) Targeting Voltage-gated potassium channel Kv11.1 (KCNH2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VESNARINONE	DMBKX3C	Cardiac failure	BD10-BD13	Approved	[3]
M100907	DM7ZFBA	Sleep-wake disorder	7A00-7B2Z	Phase 3	[4]
HP-184	DMNOMV2	Multiple sclerosis	8A40	Phase 2	[5]
NITD609	DMQHBSX	Malaria	1F40-1F45	Phase 2	[6]
ABT-229	DMN3S1B	Pain	MG30-MG3Z	Phase 2	[7]
ISOQUINE	DMR17YI	Malaria	1F40-1F45	Phase 1	[8]
Pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine derivative 1	DMC8935	N. A.	N. A.	Patented	[9]
Isoindoline derivative 5	DMIUTQW	N. A.	N. A.	Patented	[10]
Isoindoline derivative 3	DM2MYL9	N. A.	N. A.	Patented	[10]
Isoindoline derivative 4	DMP1NKI	N. A.	N. A.	Patented	[10]

Drug(s) Affected By Potassium voltage-gated channel subfamily H member 2 (KCNH2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metoclopramide	DMFA5MY	Nausea	MD90	Approved	[11]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[12]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[13]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[14]
Clarithromycin	DM4M1SG	Acute maxillary sinusitis		Approved	[14]
Disopyramide	DM5SYZP	Long QT syndrome	BC65.0	Approved	[15]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[16]
Amiodarone	DMUTEX3	Tachyarrhythmias	BC71	Approved	[17]
Dofetilide	DMPN1TW	Sinus rhythm disorder	BC9Y	Approved	[18]
Flecainide	DMSQDLE	Tachyarrhythmias	BC71	Approved	[14]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Voltage-gated potassium channel Kv11.1 (KCNH2)	TTQ6VDM	KCNH2_HUMAN	Activator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Gene/Protein Processing	[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: 7676).
• [2] Novel potent human ether-a-go-go-related gene (hERG) potassium channel enhancers and their in vitro antiarrhythmic activity. Mol Pharmacol. 2005 Sep;68(3):876-84.
• [3] Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods. Bioorg Med Chem Lett. 2003 Aug 18;13(16):2773-5.
• [4] Non-basic ligands for aminergic GPCRs: the discovery and development diaryl sulfones as selective, orally bioavailable 5-HT2A receptor antagonists ... Bioorg Med Chem Lett. 2010 Jun 15;20(12):3708-12.
• [5] Emerging drugs for spinal cord injury. Expert Opin Emerg Drugs. 2008 Mar;13(1):63-80.
• [6] Spiroindolones, a potent compound class for the treatment of malaria. Science. 2010 Sep 3;329(5996):1175-80.
• [7] 9-Dihydroerythromycin ethers as motilin agonists--developing structure-activity relationships for potency and safety. Bioorg Med Chem. 2010 Nov 1;18(21):7651-8.
• [8] Candidate selection and preclinical evaluation of N-tert-butyl isoquine (GSK369796), an affordable and effective 4-aminoquinoline antimalarial for ... J Med Chem. 2009 Mar 12;52(5):1408-15.
• [9] Towards selective phosphodiesterase 2A (PDE2A) inhibitors: a patent review (2010 - present).Expert Opin Ther Pat. 2016 Aug;26(8):933-46.
• [10] The sigma-2 (-2) receptor: a review of recent patent applications: 2013-2018.Expert Opin Ther Pat. 2018 Sep;28(9):655-663.
• [11] Comparison of the effects of metoclopramide and domperidone on HERG channels. Pharmacology. 2005 Apr;74(1):31-6. doi: 10.1159/000083234. Epub 2005 Jan 7.
• [12] Further insights into the effect of quinidine in short QT syndrome caused by a mutation in HERG. J Cardiovasc Electrophysiol. 2005 Jan;16(1):54-8. doi: 10.1046/j.1540-8167.2005.04470.x.
• [13] Automated tight seal electrophysiology for assessing the potential hERG liability of pharmaceutical compounds. Assay Drug Dev Technol. 2004 Oct;2(5):497-506. doi: 10.1089/adt.2004.2.497.
• [14] Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.
• [15] Pharmacology of the short QT syndrome N588K-hERG K+ channel mutation: differential impact on selected class I and class III antiarrhythmic drugs. Br J Pharmacol. 2008 Nov;155(6):957-66. doi: 10.1038/bjp.2008.325. Epub 2008 Aug 25.
• [16] Comparison of HERG channel blocking effects of various beta-blockers-- implication for clinical strategy. Br J Pharmacol. 2006 Mar;147(6):642-52. doi: 10.1038/sj.bjp.0706508.
• [17] Inhibitory effects of the class III antiarrhythmic drug amiodarone on cloned HERG potassium channels. Naunyn Schmiedebergs Arch Pharmacol. 1999 Mar;359(3):212-9. doi: 10.1007/pl00005344.
• [18] Redox state dependency of HERGS631C channel pharmacology: relation to C-type inactivation. FEBS Lett. 2000 May 26;474(1):111-5. doi: 10.1016/s0014-5793(00)01586-6.