99533-80-9 Usage
Description
K-252A is a staurosporine analog derived from Nocardiopsis sp. soil fungi, which is a potent inhibitor of various protein kinases, including protein kinase C (PKC), protein kinase A (PKA), Ca2+/calmodulin-dependent kinase type II, and phosphorylase kinase. It also inhibits neurotrophin receptor tyrosine kinases and has been shown to suppress trophoblast proliferation and increase apoptosis in cultured choriocarcinoma cells. Additionally, K-252A has been demonstrated to inhibit PRK1, a PKC-related kinase involved in androgen-dependent gene expression.
Uses
Used in Cell Signaling Research:
K-252A is used as a research tool to inhibit protein kinases involved in cell signaling processes, such as CaM kinase, phosphorylase kinase, serine/threonine kinases, and Trk. This helps researchers understand the roles of these kinases in cellular functions and their potential as therapeutic targets.
Used in Neurotrophin Receptor Tyrosine Kinase Inhibition:
K-252A is used to inhibit neurotrophin receptor tyrosine kinases, which play a role in the regulation of cell survival, differentiation, and proliferation. This application is useful in studying the effects of neurotrophin signaling on various cellular processes.
Used in Trophoblast Proliferation and Apoptosis Studies:
K-252A is used to suppress trophoblast proliferation and increase apoptosis in cultured choriocarcinoma cells by disrupting mitochondrial functions. This application aids in understanding the mechanisms of trophoblast cell growth and death, which are crucial for placental development and function.
Used in Androgen-Dependent Gene Expression Research:
K-252A is used to inhibit PRK1, a PKC-related kinase that phosphorylates histone H3 at threonine 11 and is involved in androgen-dependent gene expression. This application is valuable for studying the role of PRK1 in the regulation of gene expression and its potential implications in various diseases.
Used in Nerve Growth Factor (NGF) Action Inhibition:
K-252A is used to inhibit the actions of nerve growth factor (NGF) on PC12 cells, which helps researchers investigate the role of NGF in neuronal survival, growth, and differentiation.
Used in Smooth Muscle Myosin Light Chain Kinase Inhibition:
K-252A is used to inhibit smooth muscle myosin light chain kinase, which is involved in the regulation of smooth muscle contraction. This application is useful for studying the mechanisms of smooth muscle function and its potential role in various diseases.
Biological Activity
Non-selective protein kinase inhibitor; analog of staurosporine. Inhibits PKC (IC 50 = 32.9 nM), Ca 2+ /calmodulin-stimulated phosphodiesterases (IC 50 = 1.3-2.9 μ M), MLCK (K i = 20 nM) and receptor tyrosine kinases. Inhibits the oncogenic properties of MET; prevents autophosphorylation and activation of downstream effectors (MAPK, Akt).
Biochem/physiol Actions
Potent inhibitor of various protein kinases including protein kinase A, C, and G. It is is reported to selectively inhibit the actions of nerve growth factor (NGF) on PC1 2 cells and has been shown to inhibit smooth muscle myosin light chain kinase .
References
1) Kase et al. (1987), K-252 compounds, novel and potent inhibitors of protein kinase C and cyclic nucleotide-dependent protein kinases; Biochem. Biophys. Res. Commun., 142 436
2) Hashimoto et al. (1991), Potent and preferential inhibition of Ca2+/calmodulin-dependent protein kinase II by K252a and its derivative KT5926; Biochem. Biophys. Res. Commun., 181 423
3) Berg et al. (1992), K-252a inhibits nerve growth factor-induced trk proto-ooncogene tyrosine phosphorylation and kinase activity; J. Biol. Chem., 267 13
4) Ruegg et al. (1989), Staurosporine, K-252 and UCN-01: potent but non-specific inhibitors of protein kinases; Trends Pharmacol. Sci., 10 218
5) Mohri et al. (1999), K252a induces cell cycle arrest and apoptosis by inhibiting Cdc2 and Cdc25c; Cancer Invest., 17 391
Check Digit Verification of cas no
The CAS Registry Mumber 99533-80-9 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 9,9,5,3 and 3 respectively; the second part has 2 digits, 8 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 99533-80:
(7*9)+(6*9)+(5*5)+(4*3)+(3*3)+(2*8)+(1*0)=179
179 % 10 = 9
So 99533-80-9 is a valid CAS Registry Number.
InChI:InChI=1/C27H21N3O5/c1-26-27(33,25(32)34-2)11-18(35-26)29-16-9-5-3-7-13(16)20-21-15(12-28-24(21)31)19-14-8-4-6-10-17(14)30(26)23(19)22(20)29/h3-10,18,33H,11-12H2,1-2H3,(H,28,31)/t18-,26+,27+/m1/s1
99533-80-9Relevant articles and documents
Preparation of K-252a
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Page column 7, (2008/06/13)
The present invention provides a process for the synthesis of K-252a and intermediates useful in the process.
Practical Preparation of K-252a from a Fermentation Solution
Kino, Mitsutaka,Shono, Kenzo,Nishimura, Tetsuo,Nagamura, Satoru
, p. 1627 - 1629 (2007/10/03)
We developed a practical preparation procedure for K-252a by methylating K-252b on an industrial scale. The water-insoluble K-252a, which was present in the cell mass, was converted to the water-soluble K-252b Na salt in an alkaline solution. The obtained K-252b was methylated with dimethylsulfate in the presence of potassium carbonate in dimethylacetamide. We have already used this method to manufacture 90 kg of K-252b from the fermentation broth, and regenerated 65 kg of K-252a from K-252b.
Total synthesis of (+)- and (-)-K252a
Wood, John L.,Stoltz, Brian M.,Dietrich, Hans-Jürgen
, p. 10413 - 10414 (2007/10/02)
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