PINOKALANT

Details

Stereochemistry	RACEMIC
Molecular Formula	C41H48N2O9
Molecular Weight	712.8278
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C(OC)C=C2C(CCN=C2C(C(=O)N(CCC3=C(OC)C(OC)=C(OC)C=C3)CCC4=C(OC)C(OC)=C(OC)C=C4)C5=CC=CC=C5)=C1

InChI

InChIKey=PYWYBTRACMRUQV-UHFFFAOYSA-N

InChI=1S/C41H48N2O9/c1-45-31-16-14-27(37(49-5)39(31)51-7)19-22-43(23-20-28-15-17-32(46-2)40(52-8)38(28)50-6)41(44)35(26-12-10-9-11-13-26)36-30-25-34(48-4)33(47-3)24-29(30)18-21-42-36/h9-17,24-25,35H,18-23H2,1-8H3

HIDE SMILES / InChI

Molecular Formula	C41H48N2O9
Molecular Weight	712.8278
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15755315 | https://www.ncbi.nlm.nih.gov/pubmed/17446049 | https://www.ncbi.nlm.nih.gov/pubmed/11799840

Pinokalant is the isoquinoline derivative. It is a broad-spectrum cation channel blocker which inhibits store-operated cation channels in human endothelial cells, mast cells, HL60 cells and in primary cultures of cortical and hippocampal neurons. Pinokalant inhibits voltage-operated calcium channels of the L- and N-subtypes in primary cultures of cortical neurons and shows some antagonism on the NMDA- and AMPA glutamate receptor subtypes. Pinokalant also acts as an antagonist at the delayed rectifier K+ channel in PC12 cells and cortical neurons. Pinokalant reduced in vivo lesion size as well as post mortem infarct size derived from 2,3,5-triphenyltetrazolium chloride-stained brain slices 24 hr after middle cerebral artery occlusion. Pinokalant has been evaluated as a potential neuroprotectant in rodent models of stroke.

Approval Year

Targets

Primary Target	Pharmacology	Potency
delayed rectifier potassium channel activity 2 Target ID: GO:0005251 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9535721	Blocker 555	0.7 µM [IC50]
Pregnane X receptor 36 Target ID: CHEMBL3401 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20966043	Agonist 2752	3.2 µM [EC50]
cation channel activity 1 Target ID: GO:0005261 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11018702 \| https://www.ncbi.nlm.nih.gov/pubmed/11799840	Blocker 555

PubMed

Title	Date	PubMed
Calcium-activated potassium channels in insect pacemaker neurons as unexpected target site for the novel fumigant dimethyl disulfide.	2008-01	17942746
Non-selective cation channels, transient receptor potential channels and ischemic stroke.	2007-08	17446049
The broad-spectrum cation channel blocker pinokalant (LOE 908 MS) reduces brain infarct volume in rats: a temperature-controlled histological study.	2005-04	15755315
Molecular mechanisms for the activation of Ca2+-permeable nonselective cation channels by endothelin-1 in C6 glioma cells.	2003-05-01	12732355
Molecular mechanisms for the activation of voltage-independent Ca2+ channels by endothelin-1 in chinese hamster ovary cells stably expressing human endothelin(A) receptors.	2002-07	12065757
Effects of Ca(2+) influx through nonselective cation channel on noradrenaline-induced mitogenic responses.	2002-06-28	12106799
Reciprocal regulation of capacitative and non-capacitative Ca2+ entry in A7r5 vascular smooth muscle cells: only the latter operates during receptor activation.	2002-02-15	11829735
Ca(2+) channels involved in endothelin-induced mitogenic response in carotid artery vascular smooth muscle cells.	2002-02	11788344
Effects of extracellular Ca2+ influx on endothelin-1-induced intracellular mitogenic cascades in C6 glioma cells.	2002-01-25	11821017
Ca(2+) influx through nonselective cation channels plays an essential role in noradrenaline-induced arachidonic acid release in Chinese hamster ovary cells expressing alpha(1A)-, alpha(1B)-, or alpha(1D)-adrenergic receptors.	2001-12	11714874
Ca(2+) channels activated by endothelin-1 in CHO cells expressing endothelin-A or endothelin-B receptors.	2001-11	11600432
Dependency of detrusor contractions on calcium sensitization and calcium entry through LOE-908-sensitive channels.	2001-09	11522599
Ca(2+) influx through nonselective cation channels plays an essential role in endothelin-1-induced mitogenesis in C6 glioma cells.	2001-09	11522324
Failure of endothelin-1 to activate store-operated Ca2+ channels by lack of mobilization from intracellular Ca2+ stores in cultured bovine adrenal chromaffin cells.	2001-07	11485037
Characterization of Ca(2+) channels involved in endothelin-1-induced mitogenic responses in vascular smooth muscle cells.	2001-06-22	11430908
Pharmacokinetics of pinokalant, a new nonselective cation channel blocker in the rat.	2001	11799840
Potentiation of stretch-induced tone in the rabbit facial vein by an isoquinoline derivative, LOE 908.	2000-12	11138851
Pharmacological properties of calcium entry channels in A7r5 cells activated by endothelin-1.	2000-11	11078351
Broad-spectrum cation channel inhibition by LOE 908 MS reduces infarct volume in vivo and postmortem in focal cerebral ischemia in the rat.	2000	11450036

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:59:08 GMT 2025` Edited by `admin` on `Mon Mar 31 17:59:08 GMT 2025`
Record UNII	7J9ZZ971AO
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PINOKALANT

Official Name

English

LOE-908

Preferred Name

English

1-ISOQUINOLINEACETAMIDE, 3,4-DIHYDRO-6,7-DIMETHOXY-.ALPHA.-PHENYL-N,N-BIS(2-(2,3,4-TRIMETHOXYPHENYL)ETHYL)-, (±)-

Systematic Name

English

pinokalant [INN]

Common Name

English

(±)-3,4-DIHYDRO-6,7-DIMETHOXY-.ALPHA.-PHENYL-N,N-BIS(2,3,4-TRIMETHOXYPHENETHYL)-1-ISOQUINOLINEACETAMIDE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C93038