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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 of JTV-519 FREE BASE

SMILES

COC1=CC=C2SCCN(CC2=C1)C(=O)CCN3CCC(CC4=CC=CC=C4)CC3

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
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: multiple-channel blocker
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
K201 (JTV519) suppresses spontaneous Ca2+ release and [3H]ryanodine binding to RyR2 irrespective of FKBP12.6 association.
2007 Jun 15

Sample Use Guides

Atrial Fibrillation: oral tablet, x28 days or single intravenous infusionAtopic Dermatitis: Cream
Route of Administration: Other
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.
Name Type Language
JTV-519 FREE BASE
Common Name English
JTV519 FREE BASE
Code 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
Created by admin on Fri Dec 15 16:49:52 GMT 2023 , Edited by admin on Fri Dec 15 16:49:52 GMT 2023
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DRUG BANK
DB02929
Created by admin on Fri Dec 15 16:49:52 GMT 2023 , Edited by admin on Fri Dec 15 16:49:52 GMT 2023
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FDA UNII
EBY0ENK2GQ
Created by admin on Fri Dec 15 16:49:52 GMT 2023 , Edited by admin on Fri Dec 15 16:49:52 GMT 2023
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CAS
145903-06-6
Created by admin on Fri Dec 15 16:49:52 GMT 2023 , Edited by admin on Fri Dec 15 16:49:52 GMT 2023
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PUBCHEM
1715
Created by admin on Fri Dec 15 16:49:52 GMT 2023 , Edited by admin on Fri Dec 15 16:49:52 GMT 2023
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