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

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

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