ROTTLERIN

Description

Rottlerin (82-08-6) has been reported to inhibit PKCδ selectively however this result has been called into question.1?Displays neuroprotective effects.2?Induces autophagy.3?Cell permeable.

Chemical properties

orange to brown powder

The Uses of ROTTLERIN

Rottlerin is a human ether-a-go-go-related gene (hERG) potassium channel activator.

What are the applications of Application

Rottlerin is a widely-used selective inhibitor of PKCδ, CAM kinase III, and a wide range of protein kinases including PRAK and MAPKAP-K2.

Definition

ChEBI: A chromenol that is 2,2-dimethyl-2H-chromene substituted by hydroxy groups at positions 5 and 7, a 3-acetyl-2,4,6-trihydroxy-5-methylbenzyl group at position 6 and a (1E)-3-oxo-1-phenylprop-1-en-3-yl group at position 8. A potassium channel opener, it is isolated from Mallotus philippensis.

General Description

Rottlerin is extracted from Mallotus philippinensis. It is a protein kinase Cδ (PKCδ) inhibitor. Rottlerin acts as an uncoupler of mitochondrial respiration from oxidative phosphorylation. It has antitumor, autophagy, anti-proliferative, anti-metastasis and anti-invasive properties.

Biological Activity

Originally reported to inhibit PKC isoforms, with selectivity for PKC δ (K i values are 30, 42, 40, 3-6, 100, and 100 μ M for α , β , γ , δ , ε , λ respectively). Also reported to inhibit CAM kinase III. However, recently shown to inhibit a wide range of protein kinases, and most potently to inhibit PRAK and MAPKAP-K2 (IC 50 values are 1.9 and 5 μ M respectively). Also shown to act as a direct mitochondrial uncoupler.

Biochem/physiol Actions

Recently, Rottlerin (mallotoxin) has been shown to be a potent activator of the large conductance voltage and Ca2 activated K+ channel and to potently leftward shift the conductance-voltage relationship of the channel. Mallatoxin tested on hERG channels increased both step and tail hERG current by leftward shifting the voltage dependence of hERG activation and slowing channel deactivation. These actions distinguish Mallatoxin as a novel naturally occurring hERG channel activator.

Storage

+4°C

References

1) Davies et al. (2000), Specificity and mechanism of action of some commonly used protein kinase inhibitors; Biochem. J., 351 95 2) Zhang et al. (2007), Neuroprotective effect of protein kinase C delta inhibitor rottlerin in cell culture and animal models of Parkinson’s disease; J. Pharmacol. Exp. Ther., 322 913 3) Balgi et al. (2009), Screen for chemical modulators of autophagy reveals novel therapeutic inhibitors of mTORC1 signaling; PLoS One, 4 e7124