Alsterpaullone

Names

[ Name ]:
Alsterpaullone

[Synonym ]:
9-Nitro-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one
9-Nitro-7,12-dihydroindolo-[3,2-d][1]benzazepin-6(5)-one
Indolo[3,2-d][1]benzazepin-6(5H)-one, 7,12-dihydro-9-nitro-
9-nitro-7,12-dihydro-5H-indolo[3,2-d][1]benzazepin-6-one

Biological Activity

[Description]:

Alsterpaullone (9-Nitropaullone;NSC 705701) is a potent cyclin-dependent kinases (CDK) inhibitor, with IC50s of 35 nM, 15 nM, 200 nM and 40 nM for CDK1/cyclin B, CDK2/cyclin A, CDK2/cyclin E and CDK5/p35, respectively. Alsterpaullone also competes with ATP for binding to glycogen synthase kinase-3 alpha/beta (GSK-3alpha/GSK-3beta) with an IC50 of 4 nM, with antitumor activity and potential for the treatment of neurodegenerative and proliferative disorders[1].

[Related Catalog]:

Signaling Pathways >> Stem Cell/Wnt >> GSK-3

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> CDK

Signaling Pathways >> PI3K/Akt/mTOR >> GSK-3

[Target]

Cdk1/cyclin B:35 nM (IC50)

cdk2/cyclin A:15 nM (IC50)

CDK2/Cyc E:200 nM (IC50)

CDK5/p35:40 nM (IC50)

GSK-3α:4 (IC50)

GSK-3β:4 nM (IC50)

[References]

[1]. Leost M, et al. Paullones are potent inhibitors of glycogen synthase kinase-3beta and cyclin-dependent kinase 5/p25. Eur J Biochem. 2000 Oct;267(19):5983-94.

[2]. Lahusen T, et al. Alsterpaullone, a novel cyclin-dependent kinase inhibitor, induces apoptosis by activation of caspase-9 due to perturbation in mitochondrial membrane potential. Mol Carcinog. 2003 Apr;36(4):183-94.

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Boiling Point ]:
651.5±45.0 °C at 760 mmHg

[ Molecular Formula ]:
C₁₆H₁₁N₃O₃

[ Molecular Weight ]:
293.277

[ Flash Point ]:
347.8±28.7 °C

[ Exact Mass ]:
293.080048

[ PSA ]:
90.71000

[ LogP ]:
3.55

[ Vapour Pressure ]:
0.0±2.0 mmHg at 25°C

[ Index of Refraction ]:
1.738

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319-H335

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xi: Irritant;

[ Risk Phrases ]:
R36/37/38

[ Safety Phrases ]:
26-36

[ RIDADR ]:
NONH for all modes of transport

[ HS Code ]:
2933990090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles

Paullones, a series of cyclin-dependent kinase inhibitors: synthesis, evaluation of CDK1/cyclin B inhibition, and in vitro antitumor activity.

J. Med. Chem. 42 , 2909, (1999)

The paullones represent a novel class of small molecule cyclin-dependent kinase (CDK) inhibitors. To investigate structure-activity relationships and to develop paullones with antitumor activity, deri...

Evidence for antimanic efficacy of glycogen synthase kinase-3 (GSK3) inhibitors in a strain-specific model of acute mania.

Int. J. Neuropsychopharmacol. 14 , 1051-67, (2011)

There is a growing body of evidence suggesting that animal models can be developed to probe the specific domains of bipolar disorder (BD) using the endophenotype approach. Here we tested clinically ac...

Induction of canonical Wnt signaling by alsterpaullone is sufficient for oral tissue fate during regeneration and embryogenesis in Nematostella vectensis.

Dev. Dyn. 240 , 2673-9, (2011)

Although regeneration is widespread among metazoa, the molecular mechanisms have been studied in only a handful of taxa. Of these taxa, fewer still are amenable to studies of embryogenesis. Our unders...