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

General Information of Drug (ID: DMQ98RS)

• Drug Name: ML277 Drug Info
• Synonyms: ML-277; ML 277

Indication

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

• Cross-matching ID:
  PubChem CID: 53347902
  TTD Drug ID: DMQ98RS

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]
(3R,4S)-293B	DM47BEG	Discovery agent	N.A.	Investigative	[8]
HMR-1556	DMXMTA9	Discovery agent	N.A.	Investigative	[9]
R-L3	DMGEDQJ	Discovery agent	N.A.	Investigative	[10]
3S,4R-293B	DMVGDSM	Discovery agent	N.A.	Investigative	[8]
N-(3,3-Dimethyl-butyl)-4-indol-1-yl-benzamide	DMEUXOQ	Discovery agent	N.A.	Investigative	[7]

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	Activator	[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: 7666).
• [2] Identification of (R)-N-(4-(4-methoxyphenyl)thiazol-2-yl)-1-tosylpiperidine-2-carboxamide, ML277, as a novel, potent and selective K(v)7.1 (KCNQ1) potassium channel activator. Bioorg Med Chem Lett. 2012 Sep 15;22(18):5936-41.
• [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] 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.
• [9] Selective optimization of side activities: another way for drug discovery. J Med Chem. 2004 Mar 11;47(6):1303-14.
• [10] A novel benzodiazepine that activates cardiac slow delayed rectifier K+ currents. Mol Pharmacol. 1998 Jul;54(1):220-30.