142273-20-9

Basic information

• Product Name: KENPAULLONE
• Synonyms: 9-BROMO-7,12-DIHYDRO-INDOLO[3,2-D][1]BENZAZEPIN-6(5H)-ONE;8-BROMO-7,12-DIHYDRO-INDOLO[3,2-D][1]-BENZAZEPIN-6(5H)-ONE;KENPAULLONE;NSC-664704;9-Bromo-7,12-dihydro-indolo[3,2-d][1]benzazepin-6(5H)-one, NSC 664704;9-bromo-7,12-dihydro-5H-indolo[3,2-d][1]benzazepin-6-one;9-BroMopaullone;Kenpaullon
• CAS NO: 142273-20-9
• Molecular Formula: C₁₆H₁₁BrN₂O
• Molecular Weight: 327.18
• Product Categories: All Inhibitors;Inhibitors;Protein Kinase;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 142273-20-9.mol
• Article Data: 8

Chemical Properties

• Melting Point: >300°C (dec.)
• Boiling Point: 612.954 °C at 760 mmHg
• Flash Point: 324.503 °C
• Appearance: yellow/
• Density: 1.596 g/cm³
• Vapor Pressure: 5.82E-15mmHg at 25°C
• Refractive Index: 1.73
• Storage Temp.: 2-8°C
• Solubility: DMSO: 18 mg/mL, clear, yellow
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.
• CAS DataBase Reference: KENPAULLONE(CAS DataBase Reference)
• NIST Chemistry Reference: KENPAULLONE(142273-20-9)
• EPA Substance Registry System: KENPAULLONE(142273-20-9)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• Hazardous Substances Data: 142273-20-9(Hazardous Substances Data)

Usage

Description

Kenpaullone (142273-20-9) inhibits GSK-3β (IC50=0.23 μM) as well as several cyclin-dependent kinases (CDKs), IC50=0.4, 0.68 and 0.85 μM for cdk1, cdk2 and cdk5 respectively.1-3 Induces pluripotent stem cells from somatic cells4 and increases direct neural conversion of human fibroblasts5 when used with other small molecules. Inhibits Kruppel-Like Factor 4 (KLF4) reducing autoimmune arthritis in the collagen-induced arthritis mouse model.6

Chemical Properties

Tan Solid

Uses

Different sources of media describe the Uses of 142273-20-9 differently. You can refer to the following data:
1. The paullones are a novel class of kinase inhibitors, initially identified as CDK inhibitors. Kenpaullone has been found to be a useful GSK-3? inhibitor (IC50=23nM).
2. Kenpaullone has been used:as a glycogen synthase kinase 3 (GSK3)/ cyclin-dependent kinase (CDK) inhibitor to study its effects on human neural progenitor cell linesas an inhibitor of Krupple-like factor 4 (KLF4) in Gs-coupled designer GPCR (Gs DREADD= GsD) Agouti-related peptide (GsD-AgRP) miceas a GSK3/CDK inhibitor to study its effects on the sea urchin embryo development
3. The paullones are a novel class of kinase inhibitors, initially identified as CDK inhibitors. Kenpaullone has been found to be a useful GSK-3?inhibitor (IC50=23nM).

General Description

A potent, cell-permeable, and reversible inhibitor of glycogen synthase kinase-3β (IC50 = 230 nM), Lck (IC50 = 470 nM), and cyclin-dependent kinases (Cdks). Inhibits Cdk1/cyclin B (IC50 = 400 nM), Cdk2/cyclin A (IC50 = 680 nM), Cdk2/cyclin E (IC50 = 7.5 μM), and Cdk5/p25 (IC50 = 850 nM). Also inhibits other kinases such as c-Src (IC50 = 15 μM), casein kinase II (IC50 = 20 μM), ERK1 (IC50 = 20 μM), and ERK2 (IC50 = 9 μM). Inhibition is competitive with respect to ATP binding.

Biological Activity

Potent inhibitor of CDK1/cyclin B and GSK-3 β (IC 50 values are 0.4 and 0.23 μ M respectively). Also inhibits CDK2/cyclin A, CDK2/cyclin E and CDK5/cyclin/p35 (IC 50 values are 0.68, 7.5 and 0.85 μ M respectively). Selective over c-src (IC 50 = 15 μ M), casein kinase 2 (IC 50 = 20 μ M), ERK1 (IC 50 = 20 μ M), ERK2 (IC 50 = 9 μ M) and a range of other protein kinases (IC 50 values > 35 μ M). Generates induced pluripotent stem cells (iPSCs) from somatic cells when used in combination with reprogramming factors; can replace Klf4.

Biochem/physiol Actions

Kenpaullone is also an inhibitor of glycogen synthase kinase 3β (GSK3β).?It also inhibits cyclin-dependent kinase 1 (CDK1/cyclin B), CDK2/cyclin A, CDK2/cyclin E, and CDK5/p25, majorly by competitive inhibition of adenosine triphosphate (ATP) binding.

References

Zaharevitz et al. (1999), Discovery and initial characterization of the paullones, a novel class of small-molecule inhibitors of cyclin-dependent kinases; Cancer Res. 59 2566 Schultz et al. (1999) Paullones, a series of cyclin-dependent kinase inhibitor: synthesis, evaluation of CDK1/cyclin B inhibition, and in vitro antitumor activity; J.Med.Chem. 42 2909 Bain et al. (2003), The specificities of protein kinase inhibitors: an update; J. 371(Pt. 1) 199 Lyssiotis et al. (2009) Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4; Natl. Acad. Sci. USA 106 8912 Pfisterer et al. (2016), Small molecules increase direct neural conversion of human fibroblasts; Rep. 6 38290 Choi et al. (2018), Kruppel-Like Factor 4 Positively Regulates Autoimmune Arthritis in Mouse Models and Rheumatoid Arthritis in Patients via Modulating Cell Survival and Inflammation Factors of Fibroblast-Like Synoviocyte; Immunol. 9 1339

InChI:InChI=1/C16H11BrN2O/c17-9-5-6-14-11(7-9)12-8-15(20)18-13-4-2-1-3-10(13)16(12)19-14/h1-7,19H,8H2,(H,18,20)

Upstream product

• 552-89-6 2-nitro-benzaldehyde 
• 71205-21-5 methyl (E)-3-(2-amino-5-bromophenyl)prop-2-enoate 
• 615-36-1 2-bromoaniline 
• 774-14-1 (5-bromo-1H-indol-3-yl)-acetonitrile 
• 40432-84-6 (5-bromo-1H-indol-3-yl)-acetic acid 
• 830-93-3 N-[(5-bromo-1H-indol-3-yl)methyl]-N,N-dimethylamine 
• 1361550-29-9 methyl 2-(5-bromo-2-iodoindol-3-yl)acetate 
• 191171-55-8 2-anilineboronic acid pinacol ester 
• 10075-50-0 5-bromo-1H-indole 
• 117235-22-0 methyl 2-(5-bromo-1H-indole-3-yl)acetate 
• 1374335-88-2 C₁₆H₁₂BrClN₂O 
• 1391039-32-9 C₁₆H₁₀BrClN₂O₂ 
• 1374335-74-6 1,N-di(tert-butoxycarbonyl)-5-bromo-2-chloro-N-(4-methoxyphenyl)indol-3-acetamide 
• 20870-78-4 5-bromo-2-indolin-2-one 

Downstream Products

• 1213611-52-9 9-bromo-5-(3,4-dichlorobenzyl)-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one 
• 1213611-48-3 9-bromo-5-(4-methylbenzyl)-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one 
• 1213611-49-4 9-bromo-5-(4-methoxybenzyl)-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one 
• 237430-35-2 9-bromo-7,12-dihydroindolo[3,2-d ][1]benzazepin-6(5H)-thione 

Relevant articles and documents

Concise Total Syntheses of Paullone and Kenpaullone via Cyanide-Catalyzed Intramolecular Imino-Stetter Reaction

Highly concise total syntheses of paullone and kenpaullone were developed. Cyanide-catalyzed intramolecular imino-Stetter reaction of aldimines derived from methyl 2-aminocinnamate derivatives and 2-nitrobenzaldehyde provided 2-(2′-nitrophenyl)indole-3-acetic acid derivatives. Subsequent reduction of the nitro group with zinc under acidic conditions to an amino group followed by spontaneous lactam formation allowed for the total syntheses of paullone and kenpaullone to be completed in two steps starting from commercially available materials. The direct use of a nitro group as the precursor of an amino group present in the phenyl ring at the 2-position in the indole ring significantly streamlined the total syntheses of these target molecules..

Synthesis of paullone and kenpaullone derivatives by photocyclization of 2-(2-chloro-1H-indol-3-yl)-N-arylacetamides

An efficient synthesis of paullone and kenpaullone derivatives in moderate to high yields has been achieved through photocyclizations of (2-chloro-1H-indole-3-yl)-N-arylacetamides in acetone at room temperature. Paullone and kenpaullone have been obtained

Tumor-inhibiting anellated azepinone derivatives

This invention relates to anellated azepinone derivatives, a method of their production, metal complexes of the anellated azepinone derivatives as well as their use in the treatment of tumor diseases.