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

General Information of Drug (ID: DMF0CRA)

• Drug Name: zinc pyrithione Drug Info
• Synonyms: BCP13412

Indication

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

• Cross-matching ID:
  PubChem CID: 26041
  CAS Number: CAS 13463-41-7
  TTD Drug ID: DMF0CRA

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]
XE991	DMLH1PK	Discovery agent	N.A.	Investigative	[5]
N-(3,3-Dimethyl-cyclopentyl)-4-hexyloxy-benzamide	DM6EJQ4	Discovery agent	N.A.	Investigative	[6]
(3R,4S)-293B	DM47BEG	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	[7]
N-(3,3-Dimethyl-butyl)-4-indol-1-yl-benzamide	DMEUXOQ	Discovery agent	N.A.	Investigative	[6]
L-735,821	DMY60MG	Discovery agent	N.A.	Investigative	[10]

Drug(s) Targeting Voltage-gated potassium channel Kv7.5 (KCNQ5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
[14C]TEA	DM6SFYH	Discovery agent	N.A.	Investigative	[11]
XE991	DMLH1PK	Discovery agent	N.A.	Investigative	[11]
(S)-N-[1-(3-morpholin-4-yl-phenyl)-ethyl]-3-phenyl-acrylamide	DMGFOQJ	Discovery agent	N.A.	Investigative	[12]

Drug(s) Targeting Voltage-gated potassium channel Kv7.4 (KCNQ4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
[14C]TEA	DM6SFYH	Discovery agent	N.A.	Investigative	[13]
PIP2	DMOZV7N	Discovery agent	N.A.	Investigative	[14]
XE991	DMLH1PK	Discovery agent	N.A.	Investigative	[15]
(S)-N-[1-(3-morpholin-4-yl-phenyl)-ethyl]-3-phenyl-acrylamide	DMGFOQJ	Discovery agent	N.A.	Investigative	[12]
NC00075159	DMJCYMW	Discovery agent	N.A.	Investigative	[16]
ML213	DMFAUGP	Discovery agent	N.A.	Investigative	[17]

Drug(s) Targeting Voltage-gated potassium channel Kv7.2 (KCNQ2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ICA-69673	DM1RZVI	Pain	MG30-MG3Z	Preclinical	[18]
[14C]TEA	DM6SFYH	Discovery agent	N.A.	Investigative	[19]
PIP2	DMOZV7N	Discovery agent	N.A.	Investigative	[14]
PD-32577	DMBA15J	Discovery agent	N.A.	Investigative	[20]
XE991	DMLH1PK	Discovery agent	N.A.	Investigative	[21]
(S)-N-[1-(3-morpholin-4-yl-phenyl)-ethyl]-3-phenyl-acrylamide	DMGFOQJ	Discovery agent	N.A.	Investigative	[12]
QO-58	DMYXPF8	Discovery agent	N.A.	Investigative	[22]
ICA-27243	DMO0N3Q	Discovery agent	N.A.	Investigative	[23]
ztz240	DM60N3C	Discovery agent	N.A.	Investigative	[24]

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]
Voltage-gated potassium channel Kv7.2 (KCNQ2)	TTPXI3S	KCNQ2_HUMAN	Activator	[2]
Voltage-gated potassium channel Kv7.4 (KCNQ4)	TT8HGRW	KCNQ4_HUMAN	Activator	[2]
Voltage-gated potassium channel Kv7.5 (KCNQ5)	TTWVL5Q	KCNQ5_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: 2597).
• [2] Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants. Nat Chem Biol. 2007 May;3(5):287-96.
• [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] Molecular basis for differential sensitivity of KCNQ and I(Ks) channels to the cognitive enhancer XE991. Mol Pharmacol. 2000 Jun;57(6):1218-23.
• [6] 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.
• [7] 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.
• [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] KCNQ5, a novel potassium channel broadly expressed in brain, mediates M-type currents. J Biol Chem. 2000 Aug 4;275(31):24089-95.
• [12] The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels. Neuropharmacology. 2006 Nov;51(6):1068-77.
• [13] Homomeric and heteromeric assembly of KCNQ (Kv7) K+ channels assayed by total internal reflection fluorescence/fluorescence resonance energy transfer and patch clamp analysis. J Biol Chem. 2008 Nov 7;283(45):30668-76.
• [14] Regulation of Kv7 (KCNQ) K+ channel open probability by phosphatidylinositol 4,5-bisphosphate. J Neurosci. 2005 Oct 26;25(43):9825-35.
• [15] KCNQ4 channels expressed in mammalian cells: functional characteristics and pharmacology. Am J Physiol Cell Physiol. 2001 Apr;280(4):C859-66.
• [16] Identification of novel KCNQ4 openers by a high-throughput fluorescence-based thallium flux assay. Anal Biochem. 2011 Nov 1;418(1):66-72.
• [17] Discovery, Synthesis, and Structure Activity Relationship of a Series of N-Aryl- bicyclo[2.2.1]heptane-2-carboxamides: Characterization of ML213 as a Novel KCNQ2 and KCNQ4 Potassium Channel Opener. ACS Chem Neurosci. 2011 Oct 19;2(10):572-577.
• [18] Voltage-gated Potassium Channels as Therapeutic Drug Targets
• [19] Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels. Mol Pharmacol. 2000 Sep;58(3):591-600.
• [20] Synthesis and biological activity of substituted bis-(4-hydroxyphenyl)methanes as N-type calcium channel blockers. Bioorg Med Chem Lett. 1999 Aug 16;9(16):2447-52.
• [21] KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science. 1998 Dec 4;282(5395):1890-3.
• [22] Modulation of K(v)7 potassium channels by a novel opener pyrazolo[1,5-a]pyrimidin-7(4H)-one compound QO-58. Br J Pharmacol. 2013 Feb;168(4):1030-42.
• [23] The KCNQ2/3 selective channel opener ICA-27243 binds to a novel voltage-sensor domain site. Neurosci Lett. 2009 Nov 13;465(2):138-42.
• [24] Isoform-specific prolongation of Kv7 (KCNQ) potassium channel opening mediated by new molecular determinants for drug-channel interactions. J Biol Chem. 2010 Sep 3;285(36):28322-32.