ThioLox is a Competitive 15-LOX-1 Inhibitor with Anti-inflammatory and Neuroprotective Property

Arachidonic acid 15 lipoxygenases (ALOX15) is a key enzyme relevant to the synthesis of specific resolution media (SPM). Specifically, it includes lipoxygenase (LXs), decomposers (Rvs), protective elements, and maresins. 15-LOX-1, which promotes the regression of inflammation, is a nonheme iron-containing enzyme that can produce lipid peroxides from polyunsaturated fatty acids. Besides, the 15-LOX enzyme is involved in various cellular processes. Moreover, it includes cell differentiation, development, mitochondrial degradation, and reticulocyte maturation. Furthermore, 15-LOX-1 is a key enzyme relevant to oxidative stress and regulating cell death in various diseases. 15-LOX is one of the key enzymes in unsaturated fat metabolism。

Meanwhile, LOX enzymes are a family of iron (nonheme) dioxygenases that can transport oxygen molecules into free or esterified unsaturated fat acids. The next substrate of LOX is LA, which will be converted into 13-hydroxy octadecadienoic acid. Nonetheless, 15-LOX is including two isoenzymes: 15-LOX-1 and 15-LOX-2, 8. Intracellular 15-LOX activity is highly regulated. Importantly, the regulation of this enzyme occurs at different levels of transcription, translation, and post-translation in different cells. The abnormal expression of 15-LOX seems to play an indicative role in the pathology of different cancer types, tumor progression, metastasis, or cell apoptosis. Particularly, 15-LOX-1 is the main enzyme that metabolizes colon linoleic acid to 13-S-hydroxy octadecadienoic acid (13-S-HODE) and can induce cell apoptosis. Here, we will introduce a competitive 15-LOX-1 inhibitor, ThioLox.

ThioLox is a Competitive 15-LOX-1 Inhibitor with Anti-inflammatory and Neuroprotective Properties.

In the first place, ThioLox is a competitive 15-LOX-1 inhibitor with a Ki of 3.30 μM. Obviously, ThioLox shows anti-inflammatory and neuroprotective properties.

In the next place, ThioLox inhibits interleukin (IL-1β, IL-6, IL-8, IL-12b, TNFα and iNOS) expression in precision-cut lung slices (PCLS). Interestingly, ThioLox prevents lipid peroxidation and mitochondrial superoxide formation in neuronal cells.

Last but not least, ThioLox protects HT-22 cells against glutamate toxicity and significantly reduces neuronal cell death. Additionally, ThioLox has a logP of 3 and shows values that comply very well with the BBB permeability.

All in all, ThioLox is a competitive 15-LOX-1 inhibitor with anti-inflammatory and neuroprotective property.


[1] Eleftheriadis N, et al. Eur J Med Chem. 2016 Oct 21;122:786-801.