K252a

• CAT Number: I012042
• CAS Number: 99533-80-9
• Molecular Formula: C₂₇H₂₁N₃O₅
• Molecular Weight: 467.47
• Purity: ≥95%
• Target: Protein Kinase
• Solubility: Soluble in DMSO > 10 mM
• Storage: Desiccate at -20°C
• 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
• InChIKey: KOZFSFOOLUUIGY-UHOLRESSSA-N
• SMILES: CC12C(CC(O1)N3C4=CC=CC=C4C5=C6C(=C7C8=CC=CC=C8N2C7=C53)CNC6=O)(C(=O)OC)O

K252a(cas 99533-80-9) 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.  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.

Reference

1. Adv Exp Med Biol. 1996;391:367-77.
K252a and staurosporine microbial alkaloid toxins as prototype of neurotropic
drugs.
Lazarovici P(1), Rasouly D, Friedman L, Tabekman R, Ovadia H, Matsuda Y.
Author information:
(1)Department of Pharmacology and Experimental Therapeutics, School of Pharmacy,
Faculty of Medicine, Hebrew University of Jerusalem, Israel.
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.