142273-20-9 Usage
Description
KENPAULLONE is a potent, cell-permeable, and reversible inhibitor of glycogen synthase kinase-3β (GSK-3β), Lck, and cyclin-dependent kinases (Cdks). It belongs to the paullones class of kinase inhibitors, initially identified as CDK inhibitors. KENPAULLONE has demonstrated the ability to inhibit various kinases, including c-Src, casein kinase II, ERK1, and ERK2, and is competitive with respect to ATP binding. It also induces pluripotent stem cells from somatic cells and increases direct neural conversion of human fibroblasts when used with other small molecules. Additionally, it inhibits Kruppel-Like Factor 4 (KLF4), reducing autoimmune arthritis in the collagen-induced arthritis mouse model.
Uses
Used in Pharmaceutical Research:
KENPAULLONE is used as a GSK-3β/CDK inhibitor for studying its effects on human neural progenitor cell lines, the sea urchin embryo development, and as an inhibitor of KLF4 in Gs-coupled designer GPCR (Gs DREADD) Agouti-related peptide (GsD-AgRP) mice.
Used in the Biochemical Industry:
KENPAULLONE is used as a potent inhibitor of various kinases, including GSK-3β, Lck, and Cdks, for research purposes and the development of new therapeutic strategies.
Used in the Biotechnology Industry:
KENPAULLONE is used to induce pluripotent stem cells from somatic cells and increase direct neural conversion of human fibroblasts when used with other small molecules, contributing to advancements in regenerative medicine and cell therapy.
Used in the Chemical Industry:
KENPAULLONE, being a tan solid, is used in the synthesis and development of new compounds with potential applications in various fields, including pharmaceuticals and materials science.
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
Check Digit Verification of cas no
The CAS Registry Mumber 142273-20-9 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,4,2,2,7 and 3 respectively; the second part has 2 digits, 2 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 142273-20:
(8*1)+(7*4)+(6*2)+(5*2)+(4*7)+(3*3)+(2*2)+(1*0)=99
99 % 10 = 9
So 142273-20-9 is a valid CAS Registry Number.
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)
142273-20-9Relevant articles and documents
Concise Total Syntheses of Paullone and Kenpaullone via Cyanide-Catalyzed Intramolecular Imino-Stetter Reaction
Lee, Sang Eun,Lee, Seong Jong,Cheon, Cheol-Hong
, p. 4247 - 4253 (2017/09/12)
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
Li, Zhanshan,Lu, Nianhong,Wang, Lihong,Zhang, Wei
, p. 1019 - 1024 (2012/03/27)
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
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Page/Page column 6, (2010/02/15)
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.
