99533-80-9

Basic information

• Product Name: K-252A
• Synonyms: (9-alpha,10-beta,12-alpha)-este;2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-0-carboxylicacimethyl;9,1-epoxy-1h-diindolo(1,2,3-fg:3’,2’,1’-kl)pyrrolo(3,4-i)(1,6)benzodiazocine-1;antibiotick252a;antibioticsf2370;sf2370;K-252A, NOCARDIOPSIS SP;K-252A
• CAS NO: 99533-80-9
• Molecular Formula: C₂₇H₂₁N₃O₅
• Molecular Weight: 467.47
• EINECS: 200-664-3
• Product Categories: Antibiotics G-MCell Signaling and Neuroscience;Protein Kinase Inhibitors and Related ProductsKinase/Phosphatase Biology;Protein Kinase InhibitorsEnzymes, Inhibitors, and Substrates;Antibiotics;Antibiotics A to;Kinase/Phosphatase Biology;Protein Kinases and Phosphatases;Serine/Threonine Kinase Biology;Serine/Threonine Kinase Inhibitors;Protein Kinase;antibiotic
• Mol File: 99533-80-9.mol
• Article Data: 5

Chemical Properties

• Melting Point: 262-273℃ (decomposition) (methanol )
• Boiling Point: 685.3°Cat760mmHg
• Flash Point: 87℃
• Appearance: /
• Density: 1.68
• Vapor Pressure: 1.02E-19mmHg at 25°C
• Refractive Index: 1.841
• Storage Temp.: −20°C
• Solubility: DMF: 1 mg/mL
• PKA: 11.95±0.40(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months.
• CAS DataBase Reference: K-252A(CAS DataBase Reference)
• NIST Chemistry Reference: K-252A(99533-80-9)
• EPA Substance Registry System: K-252A(99533-80-9)

Safety Data

• Hazard Codes: Xi,T
• Statements: 61-20/21/22-68/20/21/22
• Safety Statements: 22-24/25-45-36/37-53
• RIDADR: NA 1993 / PGIII
• WGK Germany: 3
• RTECS: NZ0550000
• F: 8-10
• Hazardous Substances Data: 99533-80-9(Hazardous Substances Data)

Usage

Description

K252a is a staurosporine analog isolated from Nocardiopsis sp. soil fungi that inhibits protein kinase (PK) C, PKA, Ca2+/calmodulin-dependent kinase type II, and phosphorylase kinase with IC50 values of 470, 140, 270, and 1.7 nM, respectively. Because it inhibits neurotrophin receptor tyrosine kinases, K252a at 100-500 nM has been used to suppress trophoblast proliferation and increase apoptosis associated with the disruption of mitochondrial functions in cultured choriocarcinoma cells. Recently, K252a has been shown to inhibit PRK1 (IC50 = 3.2 nM in vitro), a PKC-related kinase that phosphorylates histone H3 at threonine 11 and is involved in androgen-dependent gene expression.

Uses

K-252a is used to inhibit protein kinases involved in cell signaling processes, including CaM kinase; phosphorylase kinase, serine/threonine kinases, Trk. It is used to inhibit the actions of nerve growth factor (NGF) on PC1 2 cells and to inhibit smooth muscle myosin light chain kinase .

Definition

ChEBI: A organic heterooctacyclic compound that is a potent inhibitor of protein kinase C and is isolated from Nocardiopsis sp K-252a

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

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

Upstream product

• 77-78-1 dimethyl sulfate 
• 99570-78-2 K-252b 
• 186581-53-3 diazomethane 
• 80-48-8 methyl p-toluene sulfonate 
• 183813-24-3 (2R,3R)-3-Hydroxy-2,5-dimethoxy-2-methyl-tetrahydro-furan-3-carboxylic acid methyl ester 
• 170707-32-1 6-N-(dimethoxybenzyl)-staurosporinone 
• 195709-03-6 (E)-(R)-2-Acetyl-2-hydroxy-undec-4-enoic acid methyl ester 
• 244128-10-7 C₄₅H₃₇N₃O₈ 
• 244128-14-1 C₃₃H₂₇N₃O₄Se 
• 244128-13-0 C₃₁H₂₅N₃O₃Se 
• 244128-16-3 C₂₇H₂₀IN₃O₄ 
• 244128-18-5 C₂₈H₂₀N₄O₄ 
• 244128-17-4 C₂₇H₂₁N₃O₄ 
• 244128-15-2 C₂₇H₂₁N₃O₄ 

Downstream Products

• 99570-78-2 K-252b 
• 156177-65-0 CEP-1347 
• 97161-97-2 K252a 
• 229976-32-3 C₃₉H₄₁N₃O₆SSi 
• 167468-02-2 C₃₃H₂₇N₃O₆S 
• 111358-88-4 lestaurtinib 

Relevant articles and documents

Preparation of K-252a

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

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

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