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