K-252c
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| Category | Enzyme inhibitors |
| Catalog number | BBF-03706 |
| CAS | 85753-43-1 |
| Molecular Weight | 311.34 |
| Molecular Formula | C20H13N3O |
| Purity | ≥97% |
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Description
K252c, a metabolite product of Nocardiopsis Sp., has been found to be a protein kinase C inhibitor and exhibit antiviral activities against GCV-sensitive and-resistant strains at some extent.
Specification
| Synonyms | Staurosporine aglycone; K252C; 6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-5-one |
| Storage | Store at -15°C to -20°C. Protect from light. Hygroscopic. Protect from moisture. |
| IUPAC Name | 3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4,6,8,10,15,17,19,21-nonaen-12-one |
| Canonical SMILES | C1C2=C3C4=CC=CC=C4NC3=C5C(=C2C(=O)N1)C6=CC=CC=C6N5 |
| InChI | InChI=1S/C20H13N3O/c24-20-17-12(9-21-20)15-10-5-1-3-7-13(10)22-18(15)19-16(17)11-6-2-4-8-14(11)23-19/h1-8,22-23H,9H2,(H,21,24) |
| InChI Key | MEXUTNIFSHFQRG-UHFFFAOYSA-N |
| Source | (semi)Synthetic |
Properties
| Appearance | Pale Yellow Powder |
| Application | K252c inhibits protein kinase C. Its reported IC50 value of 214 nM on rat brain enzyme K252c is cytotoxic for A549 and P388 cancer celllines showing IC50 = 2-3 μM |
| Antibiotic Activity Spectrum | viruses |
| Boiling Point | 779.0°C at 760 mmHg |
| Melting Point | >300°C |
| Density | 1.53 g/cm3 |
| Solubility | Soluble in DMSO (25 mM), and methanol. Insoluble in water. |
Reference Reading
1. Na(+)-K(+)-2Cl- cotransport, Na+/H+ exchange, and cell volume in ferret erythrocytes
C Herth, H Mairbäurl Am J Physiol . 1996 Nov;271(5 Pt 1):C1603-11. doi: 10.1152/ajpcell.1996.271.5.C1603.
Ferrets have high-Na+ and low-K+ erythrocytes (113 and 5.4 mmol/l cell water) due to the lack of Na(+)-K+ pumps. Because ferret erythrocytes have a high capacity for Na(+)-K(+)-2Cl- cotransport, the present study was undertaken to evaluate cell volume-related changes in cotransport activity and its role in volume regulation. With cell shrinkage, Na(+)-K(+)-2Cl- cotransport is activated about twofold. A large bumetanide-insensitive Na+ uptake component that has not yet been described is found in shrunken erythrocytes. Its inhibition by amiloride (concn inhibiting 50% of maximal response = 12 microM) and the Na+ dependence of amiloride-sensitive extracellular pH changes measured in cells suspended in hypertonic unbuffered medium indicate that this flux represents Na+/H+ exchange. Shrinkage activation of both transporters follows a time lag of approximately 3 min and also requires normal levels of ATP. ATP depletion inhibits Na(+)-K(+)-2Cl- cotransport even at normal cell volume. Both transporters are partially inhibited by the protein kinase inhibitors staurosporine and K252a, and activators of protein kinases A and C do not affect transport. Okadaic acid inhibition of protein phosphatases activates Na(+)-K(+)-2Cl- cotransport to its maximal activity (same after shrinkage), but shrinkage and okadaic acid activation are not additive. In contrast, okadaic acid activates Na+/H+ exchange even in shrunken cells. These results indicate that cell shrinkage activates Na(+)-K(+)-2Cl- cotransport and Na+/H+ exchange probably by phosphorylation processes.
2. Biochemical characterization and substrate specificity of the gene cluster for biosyntheses of K-252a and its analogs by in vitro heterologous expression system of Escherichia coli
Hsien-Tai Chiu, Yi-Lin Chen, Yu-Chin Lin, Meng-Na Lee, Mei-Sin Wang, Chia-Chun Lai Mol Biosyst . 2009 Oct;5(10):1192-203. doi: 10.1039/b912395b.
The indolocarbazole family of natural products has attracted great attention because of their unique structural features and potential therapeutic applications. Structurally distinct in the family, K-252a is characterized by an unusual dihydrostreptose moiety cross-bridged to K-252c aglycone with two C-N linkages. K-252a has served as a valuable lead for treatments of various cancers and neurodegenerative disorders. Recent cloning of the nok gene cluster for biosyntheses of K-252a and its analogs from Nocardiopsis sp. K-252 (NRRL15532) has revealed the nokABCD genes indispensible for K-252c biosynthesis and the key gene (nokL) coding for N-glycosylation. Herein, we report the first, successful demonstration of in vitro sugar transferase activity of indolocarbazole N-glycosyltransferase (NokL) by use of soluble protein expressed from Escherichia coli. Notably, NokL was found to exhibit peculiar mode of substrate promiscuity. Moreover, NokA and NokB reactions were biochemically characterized thoroughly by natural and alternative (e.g. fluoro-) substrates and by ammonium hydroxide (NH(4)OH). Interestingly, the in vitro expression of NokA revealed high substrate stereoselectivity, giving several indole-3-pyruvic acid-derived compounds, including indol-3-carboxaldehyde (ICA) and indole-3-acetic acid. The use of NH(4)OH successfully dissected the in vitro NokA/NokB coupled reaction, revealing mechanistic insight into the enzymes and their cross-talking relationship. Also, a simple, useful method to synthesize K-252d, ICA and chromopyrrolic acid (the NokB product) was developed by the E. coli expression systems of NokL, NokA and NokA/NokB, respectively. Together with NokA and NokB, NokL may serve as a useful tool for combinatorial engineering of K-252a and its analogs for improved therapeutic values.
3. K-252 compounds: modulators of neurotrophin signal transduction
B Knüsel, F Hefti J Neurochem . 1992 Dec;59(6):1987-96. doi: 10.1111/j.1471-4159.1992.tb10085.x.
K-252 compounds, which share a common polyaromatic aglycon structure, are rather general and potent inhibitors of various protein kinases, including protein kinase C and tyrosine-specific protein kinases, and possibly act by interfering at or near the ATP binding site. However, chemical modifications in their sugar moiety can result in high specificity of the inhibitory action and, furthermore, can induce other stimulatory and inhibitory effects on nerve cells. These compounds are of particular interest because, in intact cells, they inhibit the actions of NGF and other neurotrophins without diminishing comparable actions of other growth factors. This effect seems to reflect a direct inhibitory action on trk neurotrophin receptor proteins. At concentrations lower than those necessary to inhibit neurotrophin actions, K-252a and K-252b have been shown to potentiate the stimulatory effects of NT-3 on different neurons in culture and on PC12 cells. The structural requirements for this effect seem to be different from those for the inhibition of neurotrophin actions. These findings raise the possibility of development of compounds of high selectivity, able to inhibit or potentiate the transduction mechanisms of individual neurotrophins, and identify K-252a and K-252b as lead compounds for the development of such selective molecules. Specific inhibitors and stimulators of neurotrophins would be valuable tools to investigate biological functions of the neurotrophins in vitro and in vivo. Furthermore, it is possible that, in the future, highly selective drugs with agonistic or antagonistic actions on neurotrophin mechanisms could become therapeutically useful in the treatment of neurological disease and injury.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
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Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
