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

General Information of Drug (ID: DM47BEG)

• Drug Name: (3R,4S)-293B Drug Info
• Synonyms: LS-185874

Indication

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

• Cross-matching ID:
  PubChem CID: 121846
  ChEBI ID: CHEBI:34637
  CAS Number: CAS 163163-23-3
  TTD Drug ID: DM47BEG

Molecule-Related Drug Atlas

Drug(s) Targeting Voltage-gated potassium channel Kv7.1 (KCNQ1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Indapamide	DMGN1PW	Edema	MG29	Approved	[3]
L-768673	DMZ402C	N. A.	N. A.	Terminated	[4]
zinc pyrithione	DMF0CRA	Discovery agent	N.A.	Investigative	[5]
XE991	DMLH1PK	Discovery agent	N.A.	Investigative	[6]
N-(3,3-Dimethyl-cyclopentyl)-4-hexyloxy-benzamide	DM6EJQ4	Discovery agent	N.A.	Investigative	[7]
HMR-1556	DMXMTA9	Discovery agent	N.A.	Investigative	[8]
R-L3	DMGEDQJ	Discovery agent	N.A.	Investigative	[9]
3S,4R-293B	DMVGDSM	Discovery agent	N.A.	Investigative	[1]
N-(3,3-Dimethyl-butyl)-4-indol-1-yl-benzamide	DMEUXOQ	Discovery agent	N.A.	Investigative	[7]
L-735,821	DMY60MG	Discovery agent	N.A.	Investigative	[10]

Drug(s) Affected By Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[11]
Atenolol	DMNKG1Z	Angina pectoris	BA40	Approved	[11]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[12]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[13]
Bupivacaine	DM4PRFC	Anaesthesia	9A78.6	Approved	[14]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[15]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[16]
Mepivacaine	DMH2NMY	Analgesia	MB40.8	Approved	[14]
Mitoxantrone	DMM39BF	Acute myelogenous leukaemia	2A41	Approved	[17]
Daunorubicin	DMQUSBT	Acute monocytic leukemia		Approved	[17]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Voltage-gated potassium channel Kv7.1 (KCNQ1)	TT846HF	KCNQ1_HUMAN	Blocker (channel blocker)	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1)	OT8SPJNX	KCNQ1_HUMAN	Gene/Protein Processing	[2]

References

• [1] A kinetic study on the stereospecific inhibition of KCNQ1 and I(Ks) by the chromanol 293B. Br J Pharmacol. 2001 Dec;134(8):1647-54.
• [2] The intermediate conductance Ca2+-activated K+ channel inhibitor TRAM-34 stimulates proliferation of breast cancer cells via activation of oestrogen receptors. Br J Pharmacol. 2010 Feb 1;159(3):650-8. doi: 10.1111/j.1476-5381.2009.00557.x. Epub 2009 Dec 24.
• [3] Indapamide induces apoptosis of GH3 pituitary cells independently of its inhibition of voltage-dependent K+ currents. Eur J Pharmacol. 2006 Apr 24;536(1-2):78-84.
• [4] Class III antiarrhythmic activity in vivo by selective blockade of the slowly activating cardiac delayed rectifier potassium current IKs by (R)-2-(... J Med Chem. 1997 Nov 21;40(24):3865-8.
• [5] Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants. Nat Chem Biol. 2007 May;3(5):287-96.
• [6] Molecular basis for differential sensitivity of KCNQ and I(Ks) channels to the cognitive enhancer XE991. Mol Pharmacol. 2000 Jun;57(6):1218-23.
• [7] Design and synthesis of 4-substituted benzamides as potent, selective, and orally bioavailable I(Ks) blockers. J Med Chem. 2001 Nov 8;44(23):3764-7.
• [8] Selective optimization of side activities: another way for drug discovery. J Med Chem. 2004 Mar 11;47(6):1303-14.
• [9] A novel benzodiazepine that activates cardiac slow delayed rectifier K+ currents. Mol Pharmacol. 1998 Jul;54(1):220-30.
• [10] Molecular determinants of KCNQ1 channel block by a benzodiazepine. Mol Pharmacol. 2003 Jul;64(1):70-7.
• [11] Additional gene variants reduce effectiveness of beta-blockers in the LQT1 form of long QT syndrome. J Cardiovasc Electrophysiol. 2004 Feb;15(2):190-9. doi: 10.1046/j.1540-8167.2004.03212.x.
• [12] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [13] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [14] Long QT 1 mutation KCNQ1A344V increases local anesthetic sensitivity of the slowly activating delayed rectifier potassium current. Anesthesiology. 2006 Sep;105(3):511-20. doi: 10.1097/00000542-200609000-00015.
• [15] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [16] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [17] Identification of genomic biomarkers for anthracycline-induced cardiotoxicity in human iPSC-derived cardiomyocytes: an in vitro repeated exposure toxicity approach for safety assessment. Arch Toxicol. 2016 Nov;90(11):2763-2777.