JTV-519 FREE BASE

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C25H32N2O2S
Molecular Weight	424.599
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC2=C(SCCN(C2)C(=O)CCN3CCC(CC4=CC=CC=C4)CC3)C=C1

InChI

InChIKey=KCWGETCFOVJEPI-UHFFFAOYSA-N

InChI=1S/C25H32N2O2S/c1-29-23-7-8-24-22(18-23)19-27(15-16-30-24)25(28)11-14-26-12-9-21(10-13-26)17-20-5-3-2-4-6-20/h2-8,18,21H,9-17,19H2,1H3

HIDE SMILES / InChI

Molecular Formula	C25H32N2O2S
Molecular Weight	424.599
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19442077

Japan Tobacco developed JTV-519 (known also as K201) as an antiarrhythmic agent. This drug was in Phase II trials for the potential treatment of Atrial Fibrillation, but study was terminated. In experimental myofibrillar overcontraction models, JTV-519 demonstrated greater cardioprotectant effects than propranolol, also, this drug investigated against heart failure, but then these researches have been discontinued. In addition, K201 was in phase II clinical trial for investigation its topical implementation for Atopic Dermatitis. The mechanism of its action is both complex and controversial, known that it is a non-specific blocker of sodium, potassium and calcium channels (multiple-channel blocker). It is believed to stabilize the closed state of the RyR2 (cardiac ryanodine receptor) by increasing its affinity for the FKBP12.6 (12.6 kDa FK506 binding protein), in addition was suggested, that suppression of spontaneous Ca2 release and the activity of RyR2 contributes, at least in part, to the anti-arrhythmic properties of K201.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
multiple-channel blocker 2 Target ID: multiple-channel blocker Sources: https://www.ncbi.nlm.nih.gov/pubmed/19442077	Blocker 555

Conditions

Condition	Modality	Highest Phase	Product
Atrial fibrillation 131 Sources: https://clinicaltrials.gov/ct2/show/NCT01259622	Primary	Phase II 1147	Unknown Approved Use Unknown
Atopic dermatitis 64 Sources: https://clinicaltrials.gov/ct2/show/NCT00863005	Primary	Phase II 1147	Unknown Approved Use Unknown
heart failure 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15972811	Primary	Preclinical	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 910 P-gp 1741 MRP2 499 MRP1 116

Drug as perpetrator

Target	Modality	Activity
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=440681637	inconclusive [IC50 21.3174 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=440681637	inconclusive [IC50 23.9185 uM]
MRP1 232	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/12359358/	likely
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/12359358/ \| https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363679204	moderate [IC50 6.3209 uM]
BCRP 985	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/12359358/	no
MRP2 625	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/12359358/	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=440681637	yes [IC50 0.5355 uM]

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.sciencedirect.com/science/article/pii/S1740677305000628 \| https://pubchem.ncbi.nlm.nih.gov/bioassay/1340326#sid=174509615

PubMed

Title	Date	PubMed
K201 improves aspects of the contractile performance of human failing myocardium via reduction in Ca2+ leak from the sarcoplasmic reticulum.	2010-03	19718543
K201 (JTV519) suppresses spontaneous Ca2+ release and [3H]ryanodine binding to RyR2 irrespective of FKBP12.6 association.	2007-06-15	17313373
Protection from cardiac arrhythmia through ryanodine receptor-stabilizing protein calstabin2.	2004-04-09	15073377
JTV-519 Japan Tobacco.	2001-07	11757794

Sample Use Guides

In Vivo Use Guide

Atrial Fibrillation: oral tablet, x28 days or single intravenous infusionAtopic Dermatitis: Cream

Route of Administration: Other

In Vitro Use Guide

JTV519 was effective in reducing sarcoplasmic reticulum (SR) Ca²⁺ leak by specifically regulating ryanodine receptors (RyR2) opening at diastolic [Ca²⁺](i) in the absence of increased RyR2 phosphorylation at Ser(2814) , extending the potential use of JTV519 to conditions of acute cellular Ca²⁺ overload. SR Ca²⁺ leak was induced by ouabain in murine cardiomyocytes. [Ca²⁺]-transients, SR Ca²⁺ load and RyR2-mediated Ca²⁺ leak (sparks/waves) were quantified, with or without JTV519 (1 µmol·L⁻¹). Contribution of Ca²⁺ -/calmodulin-dependent kinase II (CaMKII) was assessed by KN-93 and Western blot (RyR2-Ser(2814) phosphorylation). Effects of JTV519 on contractile force were investigated in non-failing human ventricular trabeculae.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:36:52 GMT 2025` Edited by `admin` on `Mon Mar 31 18:36:52 GMT 2025`
Record UNII	EBY0ENK2GQ
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

JTV519 FREE BASE

Preferred Name

English

JTV-519 FREE BASE

Common Name

English

K-201 FREE BASE

Code

English

JTV 519 FREE BASE

Common Name

English

K201 FREE BASE

Common Name

English

4-(3-(1-(4-BENZYL)PIPERIDINYL)PROPIONYL)-7-METHOXY-2,3,4,5-TETRAHYDRO-1,4-BENZOTHIAZEPINE

Common Name

English

1,4-BENZOTHIAZEPINE, 2,3,4,5-TETRAHYDRO-7-METHOXY-4-(1-OXO-3-(4-(PHENYLMETHYL)-1-PIPERIDINYL)PROPYL)-

Systematic Name

English

K 201 FREE BASE

Code

English

1-PROPANONE, 1-(2,3-DIHYDRO-7-METHOXY-1,4-BENZOTHIAZEPIN-4(5H)-YL)-3-(4-(PHENYLMETHYL)-1-PIPERIDINYL)-

Systematic Name

English

Code System Code Type Description

EPA CompTox

DTXSID60163201