Target Information

Target General Information

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Target ID

T99727 (Former ID: TTDI02003)

Target Name

Hyperpolarization cyclic nucleotide-gated channel (HCN)

Gene Name

NO-GeName

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

Angina pectoris [ICD-11: BA40]

Function

Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). May mediate responses to sour stimuli.

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BioChemical Class

Voltage-gated ion channel

UniProt ID

NOUNIPROTAC

Drugs and Modes of Action

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Approved Drug(s)

[+] 1 Approved Drugs

Ivabradine

Drug Info

Approved

Angina pectoris

[2], [3], [4]

Clinical Trial Drug(s)

[+] 3 Clinical Trial Drugs

SKL-NP

Drug Info

Phase 2

Pain

[5]

ZD-7288

Drug Info

Phase 2

Angina pectoris

[6], [7]

Cilobradine

Drug Info

Phase 1

Cardiac arrhythmias

[8], [9]

Mode of Action

[+] 2 Modes of Action

Inhibitor

[+] 1 Inhibitor drugs

Ivabradine

Drug Info

[1]

Modulator

[+] 3 Modulator drugs

SKL-NP

Drug Info

[5], [10]

ZD-7288

Drug Info

[7]

Cilobradine

Drug Info

[9], [11], [12]

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

Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

References

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REF 1

Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.

REF 2

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: 2357).

REF 3

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

REF 4

ClinicalTrials.gov (NCT01373619) Heart Failure With Normal Ejection Fraction (HFNEF) in Hemodialysed Patients: Beneficial Effect of Ivabradine. U.S. National Institutes of Health.

REF 5

A Novel Carbamoyloxy Arylalkanoyl Arylpiperazine Compound (SKL-NP) Inhibits Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) Channel Currents in Rat Dorsal Root Ganglion Neurons. Korean J Physiol Pharmacol. 2012 Aug;16(4):237-41.

REF 6

REF 7

ZD 7288, an HCN channel blocker, attenuates chronic visceral pain in irritable bowel syndrome-like rats. World J Gastroenterol. 2014 Feb 28;20(8):2091-7.

REF 8

REF 9

Use-dependent blockade of cardiac pacemaker current (If) by cilobradine and zatebradine. Eur J Pharmacol. 2003 Oct 8;478(2-3):161-71.

REF 10

Korean J Physiol Pharmacol.2012 Oct;16(5):367.

REF 11

Presynaptic nitric oxide/cGMP facilitates glutamate release via hyperpolarization-activated cyclic nucleotide-gated channels in the hippocampus. Eur J Neurosci. 2011 May;33(9):1611-21.

REF 12

Population Pharmacokinetic Data Analysis of Cilobradine, an I f Channel Blocker. Pharm Res.2008 Feb;25(2):359-68.

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