K252A

K252A

* Please be kindly noted products are not for therapeutic use. We do not sell to patients.

K252A
Category New Products
Catalog number BBF-04182
CAS 99533-80-9
Molecular Weight 467.50
Molecular Formula C27H21N3O5
Purity ≥98% by HPLC

Ordering Information

Catalog Number Size Price Stock Quantity
BBF-04182 50 mg $1313 In stock

Online Inquiry

Add to cart

Description

K252a, an analog of staurosporine, has been found to be a protein kinase inhibitor and exhibit antitumor activity at some extent.

Specification

Related CAS 97161-97-2
Synonyms NZ0550000; Antibiotic K 252a
Storage Store at -20°C
IUPAC Name methyl (15S,16R,18R)-16-hydroxy-15-methyl-3-oxo-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaene-16-carboxylate
Canonical SMILES CC12C(CC(O1)N3C4=CC=CC=C4C5=C6C(=C7C8=CC=CC=C8N2C7=C53)CNC6=O)(C(=O)OC)O
InChI InChI=1S/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
InChI Key KOZFSFOOLUUIGY-IYYJOCMQSA-N
Source Nocardiopsis sp

Properties

Appearance White to Pale Yellow Powder
Antibiotic Activity Spectrum neoplastics (Tumor)
Boiling Point 685.3°C at 760 mmHg
Melting Point 255-270°C
Density 1.67 g/cm3
Solubility Soluble in chloroform, acetonitrile, acetone, dioxane, tetrahydrofuran, pyridine, ethanol, methanol, 1-propanol, ethyl acetate, n-butanol

Reference Reading

1. K252a modulates the expression of nerve growth factor-dependent capsaicin sensitivity and substance P levels in cultured adult rat dorsal root ganglion neurones
H Buck, J Winter J Neurochem . 1996 Jul;67(1):345-51. doi: 10.1046/j.1471-4159.1996.67010345.x.
K252a, an inhibitor of trk phosphorylation and nerve growth factor signal transduction in PC12 cells, blocked nerve growth factor-induced responses in cultured adult rat dorsal root ganglion sensory neurones. The nerve growth factor-dependent appearance of capsaicin sensitivity and accumulation of the neuropeptide substance P were inhibited when dorsal root ganglion neurones were grown in the presence of low concentrations (100 nM) of K252a. At higher concentrations (3 microM), however, K252a stimulated the development of capsaicin sensitivity and the accumulation of substance P even in the absence of nerve growth factor. By using a wide dose range, therefore, we showed that K252a could either inhibit or mimic nerve growth factor's actions on sensory neurones. These results may explain the apparent paradox in the literature that some groups show a blocking effect of K252a on nerve growth factor-dependent survival of dorsal root ganglion sensory neurones, whereas other report that K252a can substitute for nerve growth factor or other trophic factors and promote neuronal survival.
2. K252a and staurosporine microbial alkaloid toxins as prototype of neurotropic drugs
D Rasouly, H Ovadia, P Lazarovici, R Tabekman, L Friedman, Y Matsuda Adv Exp Med Biol . 1996;391:367-77. doi: 10.1007/978-1-4613-0361-9_31.
K252 family of alkaloid toxins-kinase inhibitors are the most widely used compounds in biological research on the role of protein kinases in cellular transduction systems, biological functions and pathophysiology of neurological disorders. The wide research interest in these toxins is due to their potency in inhibiting cellular protein kinases. However, lack of kinase specificity is one of their major drawbacks. Synthesis of new K252 derivatives can be expected to open up a new generation of kinase inhibitors. Staurosporine might be considered as a prototype neurotropic drug in view of its ability to induce neurite outgrowth and to increase tau protein levels. Because it mimics some of the neuroprotective effects of NGF and might blocks certain signals required to enhance cellular levels and/or beta amyloid processing, staurosporine might play a beneficial role in the treatment of Alzheimer's disease. The ability of staurosporine to promote neuronal regeneration and brain cholinergic neurons survival has been also demonstrated in animal studies (Nabeshima et al., 1991). The beneficial effects of K252a on the experimental autoimmune encephalomyelitis (EAE) disease mice model and it's ability to supress macrophage activation suggest an important role of protein kinases inhibitors as immunosupressive agents. These results may also point to the potential clinical relevance of K252 microbial toxins as prototypes for the development of new drugs for the management of neuronal diseases.
3. K252a and CEP1347 are neuroprotective compounds that inhibit mixed-lineage kinase-3 and induce activation of Akt and ERK
Philip A Barker, Joe Makkerh, Stephen J Morris, Geneviève Dorval, Alexandre Angers-Loustau, Mathieu Boudreau, Philippe P Roux J Biol Chem . 2002 Dec 20;277(51):49473-80. doi: 10.1074/jbc.M203428200.
K252a is best known as a Trk inhibitor, but is also a neuroprotective compound. CEP1347, a K252a derivative, retains neuroprotective properties, but does not inhibit TrkA. CEP1347 has recently been shown to directly inhibit MAPKKKs, including MLK3, but the effect of K252a on MAPKKKs remains unknown. K252a and CEP1347 not only prevent death, but also facilitate neurite outgrowth and maintenance, somal hypertrophy, and neurotransmitter synthesis. The biochemical basis for these trophic effects remains unknown. We have compared the effects of CEP1347 and K252a on MLK and JNK signaling and on neurotrophic pathways that support survival and growth. Our data show that K252a is a potent inhibitor of MLK3 activity in vivo and in vitro (IC(50) approximately 5 nm). However, we also found that K252a and CEP1347 activate Akt and ERK and show that blockade of phosphatidylinositol 3-kinase or MEK activity ablates the effect of K252a and CEP1347 on cell survival. Activation of Akt and ERK occurs through an MLK-independent pathway that may involve c-Src. Together, these data show that the neuroprotective and neurotrophic effects of K252a and CEP1347 involve activation of several neurotrophic signaling pathways.

Bio Calculators

Stock concentration: *
Desired final volume: *
Desired concentration: *

L

* 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

* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O c22h30n40
g/mol
g

Recently viewed products

Online Inquiry

Verification code
cartIcon
Inquiry Basket