237430-03-4

Alsterpaullone (237430-03-4) is a potent and selective inhibitor of GSK-3β and CDK5/p25. Potent inhibitor of CDK1/cyclin B (IC50 = 35 nM).1?Alsterpaullone induces apoptosis2 and inhibits angiogenesis3.

Alsterpaullone is a derivative of kenpaullone , an ATP-competitive inhibitor of several cyclin-dependent kinases (CDKs) as well as glycogen synthase kinase 3β (GSK3β). With slightly improved potency over kenpaullone, alsterpaullone selectively inhibits Cdk1/cyclin B, Cdk2/cyclin A, Cdk2/cyclin E, Cdk5/p25, and GSK3α/β with IC50 values of 35, 15, 200, 40, and 4 nM, respectively. Alsterpaullone has been used to inhibit the cytosolic degradation of β-catenin to alter the canonical Wnt signaling pathway in primary axis patterning, to reduce tau phosphorylation in an effort to modify neuropathological events associated with Alzheimer’s disease, and to alter cell proliferation or protein expression in various diseases.

Alsterpaullone is a potent glycogen synthase kinase-3 inhibitor and a potential therapeutic agents for treatment of Parkinson disease.

ChEBI: Alsterpaullone is an organic heterotetracyclic compound that is 1,3-dihydro-2H-1-benzazepin-2-one which shares its 4-5 bond with the 3-2 bond of 5-nitro-1H-indole. It has a role as an EC 2.7.11.22 (cyclin-dependent kinase) inhibitor, an EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor, an EC 2.7.11.26 (tau-protein kinase) inhibitor, an antineoplastic agent, an apoptosis inducer and an anti-HIV-1 agent. It is a C-nitro compound, an organic heterotetracyclic compound and a member of caprolactams. It derives from a paullone.

Alsterpaullone (ALP) is a cyclin-dependent kinase (CDK) inhibitor. It is considered as a therapeutic agent for group 3 medulloblastomas. Alsterpaullone modulates the progression of cell cycle.?It can arrest cell cycle and stimulate the apoptosis of cancer cells by activating caspase-9 through perturbation of mitochondrial membrane potential.

This cell-permeable GSK3b (FW = 293.28 g/mol; CAS 237430-03-4), also named NSC 705701 and 9-nitro-7,12-dihydroindolo[3,2-d][1]benzazepin- 6(5H)-one, targets cyclin-dependent kinases (CDKs) and glycogen synthase kinase 3b potently, reversibly, and ATP competitively. Displays remarkable antitumor activity in vitro. Alsterpaullone inhibits growth of the colon cancer cell line HCT-116, with an IC50 in the nanomolar range. Target(s): cyclin-dependent kinase, or cyclin-dependent protein kinase 2/cyclin A, IC50 = 0.08 μM; glycogen synthase kinase 3b, or [tau protein] kinase; IC50 = 0.11 μM; lymphocyte kinase, IC50 = 0.47 μM; cyclin-dependent protein kinase 1/cyclin B, IC50 = 0.035 μM; cyclin-dependent protein kinase 5/p25; mitogen-activated protein kinase; protein kinase C, weakly inhibited; cAMP-dependent protein kinase, or protein kinase A; weakly inhibited; non-specific serine/threonine protein kinase; protein-tyrosine kinase, or non-specific protein-tyrosine kinase, Lck protein-tyrosine kinase.

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1) Bain et al. (2003), The specificities of protein kinase inhibitors: an update; Biochem. J., 371 199 2) Lahusen et al. (2003), Alsterpaullone, a novel cyclin-dependent kinase inhibitor, induces apoptosis by activation of caspase-9 due to perturbation in mitochondrial membrane potential; Mol. Carcinog., 36 183 3) Zahler et al. (2010), Anti-angiogenic potential of small molecular inhibitors of cyclin dependent kinases in vitro; Angiogenesis, 13 239