Target Information

Target General Information

Target ID

T20251 (Former ID: TTDS00147)

Target Name

Voltage-gated potassium channel Kv11.1 (KCNH2)

Synonyms

hERG1; hERG-1; Voltage-gated potassium channel subunit Kv11.1; Potassium voltage-gated channel subfamily H member 2; HERG K+ channel; HERG; H-ERG; Ether-a-go-go-related protein 1; Ether-a-go-go-related gene potassium channel 1; Ether-a-go-go related protein 1; Ether-a-go-go related gene potassium channel 1; Eag related protein 1; Eag homolog; ERG-1; ERG

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Gene Name

KCNH2

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

Heart failure [ICD-11: BD10-BD1Z]

Function

Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel.

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BioChemical Class

Voltage-gated ion channel

UniProt ID

KCNH2_HUMAN

Sequence

MPVRRGHVAPQNTFLDTIIRKFEGQSRKFIIANARVENCAVIYCNDGFCELCGYSRAEVM
QRPCTCDFLHGPRTQRRAAAQIAQALLGAEERKVEIAFYRKDGSCFLCLVDVVPVKNEDG
AVIMFILNFEVVMEKDMVGSPAHDTNHRGPPTSWLAPGRAKTFRLKLPALLALTARESSV
RSGGAGGAGAPGAVVVDVDLTPAAPSSESLALDEVTAMDNHVAGLGPAEERRALVGPGSP
PRSAPGQLPSPRAHSLNPDASGSSCSLARTRSRESCASVRRASSADDIEAMRAGVLPPPP
RHASTGAMHPLRSGLLNSTSDSDLVRYRTISKIPQITLNFVDLKGDPFLASPTSDREIIA
PKIKERTHNVTEKVTQVLSLGADVLPEYKLQAPRIHRWTILHYSPFKAVWDWLILLLVIY
TAVFTPYSAAFLLKETEEGPPATECGYACQPLAVVDLIVDIMFIVDILINFRTTYVNANE
EVVSHPGRIAVHYFKGWFLIDMVAAIPFDLLIFGSGSEELIGLLKTARLLRLVRVARKLD
RYSEYGAAVLFLLMCTFALIAHWLACIWYAIGNMEQPHMDSRIGWLHNLGDQIGKPYNSS
GLGGPSIKDKYVTALYFTFSSLTSVGFGNVSPNTNSEKIFSICVMLIGSLMYASIFGNVS
AIIQRLYSGTARYHTQMLRVREFIRFHQIPNPLRQRLEEYFQHAWSYTNGIDMNAVLKGF
PECLQADICLHLNRSLLQHCKPFRGATKGCLRALAMKFKTTHAPPGDTLVHAGDLLTALY
FISRGSIEILRGDVVVAILGKNDIFGEPLNLYARPGKSNGDVRALTYCDLHKIHRDDLLE
VLDMYPEFSDHFWSSLEITFNLRDTNMIPGSPGSTELEGGFSRQRKRKLSFRRRTDKDTE
QPGEVSALGPGRAGAGPSSRGRPGGPWGESPSSGPSSPESSEDEGPGRSSSPLRLVPFSS
PRPPGEPPGGEPLMEDCEKSSDTCNPLSGAFSGVSNIFSFWGDSRGRQYQELPRCPAPTP
SLLNIPLSSPGRRPRGDVESRLDALQRQLNRLETRLSADMATVLQLLQRQMTLVPPAYSA
VTTPGPGPTSTSPLLPVSPLPTLTLDSLSQVSQFMACEELPPGAPELPQEGPTRRLSLPG
QLGALTSQPLHRHGSDPGS

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3D Structure

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PDB

ADReCS ID

BADD_A04352 ; BADD_A04830

HIT2.0 ID

T59P8I

Drugs and Modes of Action

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Approved Drug(s)

[+] 1 Approved Drugs

VESNARINONE

Drug Info

Approved

Cardiac failure

[2]

Clinical Trial Drug(s)

[+] 5 Clinical Trial Drugs

M100907

Drug Info

Phase 3

Sleep-wake disorder

[3]

ABT-229

Drug Info

Phase 2

Pain

[4], [5]

HP-184

Drug Info

Phase 2

Multiple sclerosis

[6]

NITD609

Drug Info

Phase 2

Malaria

[7]

ISOQUINE

Drug Info

Phase 1

Malaria

[8]

Discontinued Drug(s)

[+] 3 Discontinued Drugs

MK-499

Drug Info

Discontinued in Phase 2

Cardiac arrhythmias

[9], [10]

Bertosamil

Drug Info

Terminated

Angina pectoris

[11]

L-702958

Drug Info

Terminated

Cardiac arrhythmias

[12]

Mode of Action

[+] 7 Modes of Action

Inhibitor

[+] 69 Inhibitor drugs

VESNARINONE

Drug Info

[1]

M100907

Drug Info

[13]

ABT-229

Drug Info

[14]

NITD609

Drug Info

[15]

ISOQUINE

Drug Info

[16]

Pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine derivative 1

Drug Info

[18]

Pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine derivative 2

Drug Info

[18]

MK-499

Drug Info

[20]

(1R,5R)-30-OXO-19-OXA-2,6,10,12-TETRAAZAHEXACYCLO[18.6.2.1^{2,5}.1^{14,18}.0^{8,12}.0^{23,27}]TRIACONTA-8,10,14(29),15,17,20(28),21,23(27)-OCTAENE-17-CARBONITRILE (STRUCTURAL MIX)

Drug Info

[22]

(2R)-N-(6-(4-CHLOROPHENYL)-7-(2,4-DICHLOROPHENYL)-2,2-DIMETHYL-3,4-DIHYDRO-2H-PYRANO[2,3-B]PYRIDIN-4-YL)-2-HYDROXYPROPANAMIDE (ENANTIOMERIC MIX)

Drug Info

[23]

(E)-2-(4-fluorostyryl)-5-(phenylsulfinyl)pyridine

Drug Info

[24]

(R)-3-(naphthalen-2-ylmethoxy)pyrrolidine

Drug Info

[25]

(R)-6-(2-(2-methylpyrrolidin-1-yl)ethyl)quinoline

Drug Info

[26]

(R)-N-isobutyl-N-(pyrrolidin-3-yl)-2-naphthamide

Drug Info

[27]

(R)-ONDANSETRON

Drug Info

[28]

(S)-3-(naphthalen-2-ylmethoxy)pyrrolidine

Drug Info

[25]

1,6-bis(4-(3-chlorophenyl)piperazin-1-yl)hexane

Drug Info

[29]

1,6-bis(4-(3-methoxyphenyl)piperazin-1-yl)hexane

Drug Info

[29]

1,6-bis(4-m-tolylpiperazin-1-yl)hexane

Drug Info

[29]

1,6-bis(4-phenylpiperazin-1-yl)hexane

Drug Info

[29]

1-(1-(2-FLUOROPHENYL)-2-(2-(TRIFLUOROMETHOXY)PHENYL)ETHYL)PIPERAZINE (ENANTIOMERIC MIX)

Drug Info

[30]

1-(1-(4-FLUOROPHENYL)-2-(2-(TRIFLUOROMETHOXY)PHENYL)ETHYL)PIPERAZINE (ENANTIOMERIC MIX)

Drug Info

[30]

1-(1-phenyl-2-(2-propoxyphenyl)ethyl)piperazine

Drug Info

[30]

1-(2-(2-(DIFLUOROMETHOXY)PHENYL)-1-PHENYLETHYL)PIPERAZINE (ENANTIOMERIC MIX)

Drug Info

[30]

1-(2-(6-fluoronaphthalen-2-yl)ethyl)piperazine

Drug Info

[25]

1-(4-p-Tolyl-butyl)-piperidine

Drug Info

[31]

2-Phenyl-3-piperidin-3-yl-1H-indole

Drug Info

[32]

2-Phenyl-3-piperidin-4-yl-1H-indole

Drug Info

[32]

2-[4-(2-Piperidin-1-ylethyl)phenoxy]benzothiazole

Drug Info

[33]

3 9-DIHYDRO-N-DESMETHYL-N-ISOPROPYLERYTHROMYCIN A

Drug Info

[14]

3-(1-Benzyl-piperidin-3-yl)-2-phenyl-1H-indole

Drug Info

[32]

3-(1-Methyl-piperidin-2-yl)-2-phenyl-1H-indole

Drug Info

[32]

3-(1-Methyl-piperidin-3-yl)-2-phenyl-1H-indole

Drug Info

[32]

3-(1-Phenethyl-piperidin-3-yl)-2-phenyl-1H-indole

Drug Info

[32]

3-(1-Phenethyl-piperidin-4-yl)-2-phenyl-1H-indole

Drug Info

[32]

3-(1H-indol-3-yl)-N-methyl-3-phenylpropan-1-amine

Drug Info

[34]

3-(benzo[b]thiophen-5-yl)-3-benzylpyrrolidine

Drug Info

[34]

3-(dimethylamino)-1-(4-heptylphenyl)propan-1-one

Drug Info

[35]

4-((naphthalen-2-yloxy)methyl)piperidine

Drug Info

[25]

4-(2-thienyl)benzene-1,2-diamine

Drug Info

[36]

4-(3-thienyl)benzene-1,2-diamine)

Drug Info

[36]

4-(p-Tolyl)spiro[chromene-2,4'-piperidine]

Drug Info

[37]

4-(Spiro[chromene-2,4'-piperidine]-4-yl)benzamide

Drug Info

[38]

4-(Spiro[chromene-2,4'-piperidine]-4-yl)phenol

Drug Info

[37]

4-Benzenesulfonyl-1-(3-phenyl-propyl)-piperidine

Drug Info

[39]

4-Benzenesulfonyl-1-phenethyl-piperidine

Drug Info

[39]

4-Phenylspiro[chromene-2,4'-piperidine]

Drug Info

[37]

5-(3-(4-fluorobenzyl)pyrrolidin-3-yl)-1H-indole

Drug Info

[34]

5-(3-benzylpyrrolidin-3-yl)-1-methyl-1H-indole

Drug Info

[34]

5-(3-benzylpyrrolidin-3-yl)-1h-indole (structural mix)

Drug Info

[34]

5-(3-butylpyrrolidin-3-yl)-1H-indole

Drug Info

[34]

5-Chloro-3-ethyl-1-(4-fluoro-phenyl)-1H-indole

Drug Info

[20]

6-(4-CHLOROPHENYL)-7-(2,4-DICHLOROPHENYL)-N-(HYDROXYMETHYL)-1,2,2-TRIMETHYL-1,2,3,4-TETRAHYDRO-1,8-NAPHTHYRIDINE-4-CARBOXAMIDE (ENANTIOMERIC MIX)

Drug Info

[23]

7-(piperidin-4-ylmethoxy)-2-naphthonitrile

Drug Info

[25]

8-azabicyclo[3.2.1]octan-3-yloxy-benzamide

Drug Info

[40]

ADS-103253

Drug Info

[42]

BMS-645737

Drug Info

[43]

DESMETHYLOLANZAPINE

Drug Info

[22]

GW803430

Drug Info

[46]

JNJ-10392980

Drug Info

[33]

MDL-74156

Drug Info

[1]

MK-1925

Drug Info

[49]

N-(4-(benzyloxy)phenethyl)pyridin-4-amine

Drug Info

[50]

N-(6-(4-CHLOROPHENYL)-7-(2,4-DICHLOROPHENYL)-2,2-DIMETHYL-3,4-DIHYDRO-2H-PYRANO[2,3-B]PYRIDIN-4-YL)-3-HYDROXYPROPANAMIDE (ENANTIOMERIC MIX)

Drug Info

[23]

N-(piperidin-4-yl)-N-propyl-2-naphthamide

Drug Info

[27]

N-[6-(4-CHLOROPHENYL)-7-(2,4-DICHLOROPHENYL)-2,2-DIMETHYL-3,4-DIHYDRO-2H-PYRANO[2,3-B]PYRIDINE-4-YL]-4,4,4-TRIFLUORO-3-HYDROXYBUTANAMIDE (DIASTEREOMERIC MIX)

Drug Info

[51]

PF-526014

Drug Info

[30]

R-dimethindene

Drug Info

[55]

[1-(4-p-Tolyl-butyl)-piperidin-4-yl]-methanol

Drug Info

[31]

Blocker

[+] 2 Blocker drugs

HP-184

Drug Info

[6]

Desmethylastemizole

Drug Info

[1], [44]

Ligand

[+] 5 Ligand drugs

Isoindoline derivative 1

Drug Info

[17]

Isoindoline derivative 2

Drug Info

[17]

Isoindoline derivative 3

Drug Info

[17]

Isoindoline derivative 4

Drug Info

[17]

Isoindoline derivative 5

Drug Info

[17]

Antagonist

[+] 3 Antagonist drugs

Quinoline derivative 11

Drug Info

[19]

Quinoline derivative 12

Drug Info

[19]

Quinoline derivative 13

Drug Info

[19]

Modulator

[+] 2 Modulator drugs

Bertosamil

Drug Info

[11]

L-702958

Drug Info

[21]

Activator

[+] 8 Activator drugs

A-935142

Drug Info

[41]

ginsenoside Rg3

Drug Info

[45]

ICA-105574

Drug Info

[47]

KB-130015

Drug Info

[48]

PD-118057

Drug Info

[53]

PD-307243

Drug Info

[54]

RPR260243

Drug Info

[56]

VU0405601

Drug Info

[57]

Opener

[+] 1 Opener drugs

NS-1643

Drug Info

[52]

Cell-based Target Expression Variations

Top

Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Biological Network Descriptors

Different Human System Profiles of Target

Top

Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Biological Network Descriptors

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Potassium channel subfamily K member 17 (KCNK17)	PF07885	26.471 (18/68)	1.00E-03

Degree	5	Degree centrality	5.37E-04	Betweenness centrality	1.07E-03
Closeness centrality	2.25E-01	Radiality	1.40E+01	Clustering coefficient	2.00E-01
Neighborhood connectivity	3.16E+01	Topological coefficient	2.07E-01	Eccentricity	11
Download	Click to Download the Full PPI Network of This Target

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

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Co-Targets

Co-Targets Info

Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

Target-interacting Proteins

Target-interacting Proteins Info

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

Top

Pathwhiz Pathway

[+] 1 Pathwhiz Pathways

Muscle/Heart Contraction

Reactome

[+] 1 Reactome Pathways

Voltage gated Potassium channels

WikiPathways

[+] 3 WikiPathways

SIDS Susceptibility Pathways

Hematopoietic Stem Cell Differentiation

Potassium Channels

Target-Related Models and Studies

Top

Target Validation

Target Validation Info

References

Top

REF 1

Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods. Bioorg Med Chem Lett. 2003 Aug 18;13(16):2773-5.

REF 2

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

REF 3

ClinicalTrials.gov (NCT00495885) Efficacy and Safety of M100907 on Sleep Maintenance Insomnia With a Sub-study in Stable Type II Diabetes Mellitus. U.S. National Institutes of Health.

REF 4

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: 1444).

REF 5

GSK962040: a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility. Neurogastroenterol Motil. 2009 Jun;21(6):657-64, e30-1.

REF 6

Emerging drugs for spinal cord injury. Expert Opin Emerg Drugs. 2008 Mar;13(1):63-80.

REF 7

ClinicalTrials.gov (NCT01836458) A Study to Find the Minimum Inhibitory Concentration of KAE609 in Adult Male Patients With P. Falciparum Monoinfection. U.S. National Institutes of Health.

REF 8

Antimalarial activity of isoquine against Kenyan Plasmodium falciparum clinical isolates and association with polymorphisms in pfcrt and pfmdr1 genes. J Antimicrob Chemother. 2013 Apr;68(4):786-8.

REF 9

REF 10

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002963)

REF 11

Bertosamil blocks HERG potassium channels in their open and inactivated states. Br J Pharmacol. 2002 Sep;137(2):221-8.

REF 12

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002728)

REF 13

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.

REF 14

9-Dihydroerythromycin ethers as motilin agonists--developing structure-activity relationships for potency and safety. Bioorg Med Chem. 2010 Nov 1;18(21):7651-8.

REF 15

Spiroindolones, a potent compound class for the treatment of malaria. Science. 2010 Sep 3;329(5996):1175-80.

REF 16

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.

REF 17

The sigma-2 (-2) receptor: a review of recent patent applications: 2013-2018.Expert Opin Ther Pat. 2018 Sep;28(9):655-663.

REF 18

Towards selective phosphodiesterase 2A (PDE2A) inhibitors: a patent review (2010 - present).Expert Opin Ther Pat. 2016 Aug;26(8):933-46.

REF 19

P2X7 receptor antagonists: a patent review (2010-2015).Expert Opin Ther Pat. 2017 Mar;27(3):257-267.

REF 20

Characterization of HERG potassium channel inhibition using CoMSiA 3D QSAR and homology modeling approaches. Bioorg Med Chem Lett. 2003 May 19;13(10):1829-35.

REF 21

Analogs of MK-499 are differentially affected by a mutation in the S6 domain of the hERG K+ channel.Biochem Pharmacol.2009 May 15;77(10):1602-11.

REF 22

Side chain flexibilities in the human ether-a-go-go related gene potassium channel (hERG) together with matched-pair binding studies suggest a new ... J Med Chem. 2009 Jul 23;52(14):4266-76.

REF 23

Dihydro-pyrano[2,3-b]pyridines and tetrahydro-1,8-naphthyridines as CB1 receptor inverse agonists: synthesis, SAR and biological evaluation. Bioorg Med Chem Lett. 2010 Jun 15;20(12):3750-4.

REF 24

2,5-Disubstituted pyridines: the discovery of a novel series of 5-HT2A ligands. Bioorg Med Chem Lett. 2007 May 1;17(9):2643-8.

REF 25

Design and optimization of selective serotonin re-uptake inhibitors with high synthetic accessibility. Part 1. Bioorg Med Chem Lett. 2009 Apr 15;19(8):2329-32.

REF 26

In vitro studies on a class of quinoline containing histamine H3 antagonists. Bioorg Med Chem Lett. 2010 Jun 1;20(11):3295-300.

REF 27

Bioorg Med Chem Lett. 2009 Oct 15;19(20):5893-7. Epub 2009 Aug 21.Design and optimisation of selective serotonin re-uptake inhibitors with high synthetic accessibility: part 2.

REF 28

A binary QSAR model for classification of hERG potassium channel blockers. Bioorg Med Chem. 2008 Apr 1;16(7):4107-19.

REF 29

Discovery of bishomo(hetero)arylpiperazines as novel multifunctional ligands targeting dopamine D(3) and serotonin 5-HT(1A) and 5-HT(2A) receptors. J Med Chem. 2010 Jun 24;53(12):4803-7.

REF 30

Second generation N-(1,2-diphenylethyl)piperazines as dual serotonin and noradrenaline reuptake inhibitors: improving metabolic stability and reduc... Bioorg Med Chem Lett. 2010 Jun 15;20(12):3788-92.

REF 31

Structural determinants for histamine H(1) affinity, hERG affinity and QTc prolongation in a series of terfenadine analogs. Bioorg Med Chem Lett. 2009 Sep 1;19(17):5043-7.

REF 32

3-(4-Fluoropiperidin-3-yl)-2-phenylindoles as high affinity, selective, and orally bioavailable h5-HT(2A) receptor antagonists. J Med Chem. 2001 May 10;44(10):1603-14.

REF 33

Identification of a potent, selective, and orally active leukotriene a4 hydrolase inhibitor with anti-inflammatory activity. J Med Chem. 2008 Jul 24;51(14):4150-69.

REF 34

Novel 3,3-disubstituted pyrrolidines as selective triple serotonin/norepinephrine/dopamine reuptake inhibitors. Bioorg Med Chem Lett. 2008 Dec 1;18(23):6062-6.

REF 35

Improvement of pharmacological properties of irreversible thyroid receptor coactivator binding inhibitors. J Med Chem. 2009 Jul 9;52(13):3892-901.

REF 36

Parallel medicinal chemistry approaches to selective HDAC1/HDAC2 inhibitor (SHI-1:2) optimization. Bioorg Med Chem Lett. 2009 Feb 15;19(4):1168-72.

REF 37

Potent, orally bioavailable delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-4-(5-hydroxyspiro[chromene-2,4'-pipe... J Med Chem. 2008 Oct 9;51(19):5893-6.

REF 38

Spirocyclic delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-3-hydroxy-4-(spiro[chromene-2,4'-piperidine]-4-yl) b... J Med Chem. 2009 Sep 24;52(18):5685-702.

REF 39

4-(Phenylsulfonyl)piperidines: novel, selective, and bioavailable 5-HT(2A) receptor antagonists. J Med Chem. 2002 Jan 17;45(2):492-503.

REF 40

SAR development of a series of 8-azabicyclo[3.2.1]octan-3-yloxy-benzamides as kappa opioid receptor antagonists. Part 2. Bioorg Med Chem Lett. 2010 Sep 15;20(18):5405-10.

REF 41

Electrophysiologic characterization of a novel hERG channel activator. Biochem Pharmacol. 2009 Apr 15;77(8):1383-90.

REF 42

Quinazoline and benzimidazole MCH-1R antagonists. Bioorg Med Chem Lett. 2007 Mar 1;17(5):1403-7.

REF 43

Discovery and preclinical studies of 5-isopropyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)-N-(2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]t... Bioorg Med Chem Lett. 2008 May 1;18(9):2985-9.

REF 44

Block of HERG potassium channels by the antihistamine astemizole and its metabolites desmethylastemizole and norastemizole. J Cardiovasc Electrophysiol. 1999 Jun;10(6):836-43.

REF 45

Ginsenoside Rg(3) decelerates hERG K(+) channel deactivation through Ser631 residue interaction. Eur J Pharmacol. 2011 Aug 1;663(1-3):59-67.

REF 46

Novel approach for chemotype hopping based on annotated databases of chemically feasible fragments and a prospective case study: new melanin concen... J Med Chem. 2009 Apr 9;52(7):2076-89.

REF 47

Pharmacological removal of human ether- -go-go-related gene potassium channel inactivation by 3-nitro-N-(4-phenoxyphenyl) benzamide (ICA-105574). Mol Pharmacol. 2010 Jan;77(1):58-68.

REF 48

The amiodarone derivative KB130015 activates hERG1 potassium channels via a novel mechanism. Eur J Pharmacol. 2010 Apr 25;632(1-3):52-9.

REF 49

Identification of MK-1925: a selective, orally active and brain-penetrable opioid receptor-like 1 (ORL1) antagonist. Bioorg Med Chem Lett. 2009 Aug 15;19(16):4729-32.

REF 50

Identification and characterization of 4-methylbenzyl 4-[(pyrimidin-2-ylamino)methyl]piperidine-1-carboxylate, an orally bioavailable, brain penetr... J Med Chem. 2007 Feb 22;50(4):807-19.

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