Shikonin is a specific inhibitor of the IKKβ/NEMO complex PPI with IC50 of 170 nM, also a potent TMEM16A chloride channel inhibitor (IC50=6.5 uM) and specific pyruvate kinase M2 (PKM2) inhibitor.
Shikonin possesses various physiological and pharmacological properties, including anti-inflammatory, wound healing, and anti-cancer effects.
Shikonin suppresses the malignant phenotypes of colorectal cancer cells in vitro and in vivo, decreases the protein levels Cyclin E1/D1, CDK4 and MMP2/9, while increasing the levels of cleaved caspases 3 and 9, cleaved PARP, and TIMP.
Shikonin shows no effects on the upstream regulators of IKKβ/NEMO complex.
Shikonin effectively impairs NEMO/IKKβ interaction with IC50 of 231.03 nM in fluorescence resonance energy transfer (FRET) assays.
Shikonin is a natural product and is a bioactive constituent of Lithospermum erythrorhizon, which has a long history of more than 2000 years of use as a Chinese medicinal herb known as zicao.