AS-601245

Details

Stereochemistry	RACEMIC
Molecular Formula	C20H16N6S
Molecular Weight	372.446
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

N#CC(C1=NC2=CC=CC=C2S1)C3=NC(NCCC4=CC=CN=C4)=NC=C3

InChI

InChIKey=RCYPVQCPYKNSTG-UHFFFAOYSA-N

InChI=1S/C20H16N6S/c21-12-15(19-25-17-5-1-2-6-18(17)27-19)16-8-11-24-20(26-16)23-10-7-14-4-3-9-22-13-14/h1-6,8-9,11,13,15H,7,10H2,(H,23,24,26)

HIDE SMILES / InChI

Molecular Formula	C20H16N6S
Molecular Weight	372.446
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/14988419 | https://www.ncbi.nlm.nih.gov/pubmed/15999997https://www.ncbi.nlm.nih.gov/pubmed/14988419
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/15210584 | https://www.ncbi.nlm.nih.gov/pubmed/15715656 | https://www.ncbi.nlm.nih.gov/pubmed/19947601 | https://www.ncbi.nlm.nih.gov/pubmed/16972261

AS601245 (1,3-benzothiazol-2-yl (2-{[2-(3-pyridinyl) ethyl] amino}-4 pyrimidinyl) acetonitrile) is a potent and selective JNK inhibitor developed by Applied Research Systems ARS Holding as promising neuroprotective agent. In vitro AS601245 is a potent and cell permeable ATP competitive JNK inhibitor, which has been shown to inhibit the JNK signaling pathway, promotes cell survival after cerebral ischemia. AS601245 and clofibrate have a synergistic effect in inducing cell responses and in affecting the gene expression profile in CaCo-2 colon cancer cells. AS601245 is a new potent adenosine triphosphate-competitive JNK inhibitor, provides significant protection against the delayed loss of hippocampal CA1 neurons in a gerbil model of transient global ischemia and is also neuroprotective in rats after focal cerebral ischemia. The ischemia-induced phospho-c-Jun expression is attenuated by AS601245, providing a mechanism through which AS601245 blocks the loss of neuronal cells.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
c-Jun N-terminal kinase 1 8 Target ID: CHEMBL2276 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14988419	Inhibitor 8297	0.15 µM [IC50]
c-Jun N-terminal kinase 2 4 Target ID: CHEMBL4179 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14988419	Inhibitor 8297	0.22 µM [IC50]
c-Jun N-terminal kinase 3 5 Target ID: CHEMBL2637 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14988419	Inhibitor 8297	0.07 µM [IC50]
Mitogen-activated protein kinase 10 3 Target ID: P53779 Gene ID: 5602.0 Gene Symbol: MAPK10 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/14988419	Inhibitor 8297	70.0 nM [IC50]
Mitogen-activated protein kinase 8 3 Target ID: P45983\|\|\|Q308M2 Gene ID: 5599.0 Gene Symbol: MAPK8 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/14988419	Inhibitor 8297	150.0 nM [IC50]
Mitogen-activated protein kinase kinase kinase 9 5 Target ID: P80192 Gene ID: 4293.0 Gene Symbol: MAP3K9 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/14988419	Inhibitor 8297	220.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Ischemic insult 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14988419	Primary	Basic research	Unknown Approved Use Unknown
Parkinson's disease 226 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15723614	Primary	Basic research	Unknown Approved Use Unknown
Cerebral ischemia 8 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14988419	Primary	Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
AS601245 (1,3-benzothiazol-2-yl (2-[[2-(3-pyridinyl) ethyl] amino]-4 pyrimidinyl) acetonitrile): a c-Jun NH2-terminal protein kinase inhibitor with neuroprotective properties.	2004 Jul	14988419
Inhibition of c-Jun N-terminal kinase decreases cardiomyocyte apoptosis and infarct size after myocardial ischemia and reperfusion in anaesthetized rats.	2004 Jul	15210584
Control of death receptor and mitochondrial-dependent apoptosis by c-Jun N-terminal kinase in hippocampal CA1 neurones following global transient ischaemia.	2005 Mar	15715656
AS601245, a c-Jun NH2-terminal kinase (JNK) inhibitor, reduces axon/dendrite damage and cognitive deficits after global cerebral ischaemia in gerbils.	2008 Jan	18026128
Rosiglitazone and AS601245 decrease cell adhesion and migration through modulation of specific gene expression in human colon cancer cells.	2012	22761953
AS601245, an Anti-Inflammatory JNK Inhibitor, and Clofibrate Have a Synergistic Effect in Inducing Cell Responses and in Affecting the Gene Expression Profile in CaCo-2 Colon Cancer Cells.	2012	22619672

Patents

Sample Use Guides

In Vivo Use Guide

AS601245 was injected as an i.v. bolus dose (1 mg/kg) at the initiation of reperfusion followed by an i.v. infusion (0.6 mg/kg/h) during 22h.

Route of Administration: Intravenous

In Vitro Use Guide

PC12 cells were incubated with 1uM rotenone for 24, 36 and 48 h. AS601245 at 2 uM was added to the medium 2 h prior to 1 uM rotenone exposure. AS601245 almost completely prevented the apoptosis inducing factor release.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 10:04:47 UTC 2023` Edited by `admin` on `Sat Dec 16 10:04:47 UTC 2023`
Record UNII	Y9A2N9O85G
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AS-601245

Common Name

English

2-BENZOTHIAZOLEACETONITRILE, .ALPHA.-(2-((2-(3-PYRIDINYL)ETHYL)AMINO)-4-PYRIMIDINYL)-

Systematic Name

English

AS601245

Code

English

SAPK INHIBITOR V

Common Name

English

JNK INHIBITOR V

Common Name

English

Code System Code Type Description

CAS

861411-83-8