5-Lipoxygenase

5-lipoxygenase (5-LO) pathway is the major source of potent proinflammatory leukotrienes (LTs) issued from the metabolism of arachidonic acid (AA), and best known for their roles in the pathogenesis of asthma. These lipid mediators are mainly released from myeloid cells and may act as physiological autocrine and paracrine signalling molecules, and play a central role in regulating the interaction between innate and adaptive immunity.

PGS-IN-1
102271-49-8
1029317-21-2
PF04191834
1029317-21-2
111406-87-2
Zileuton
111406-87-2
118569-21-4
Zileuton sodium
118569-21-4
119256-94-9
FR 110302
119256-94-9
120210-48-2
Tenidap
120210-48-2
121502-05-4
PD 127443
121502-05-4
129424-08-4
ICI 211965
129424-08-4
132392-65-5
LY 269415
132392-65-5
2-TEDC
132465-10-2
132956-22-0
Enazadrem phosphate
132956-22-0
1532593-30-8
ML355
1532593-30-8
COX/5-LO-IN-1
154355-75-6
CMI-392
205654-37-1
PD 146176
4079-26-9

Background


An Overview of 5-lipoxygenase

5-lipoxygenase (5-LOX) is an important kind of dioxygenase and a kind of LOX isozyme in organism. It is widely found in the tissues and blood of most mammals. The molecular weight of 5-lipoxygenase is 75 ~ 80kD, including 673 amino acids. 5-LOX mainly consists of two domains, of which the C2 domain, which is composed of 120 amino acids at the N-terminal, can bind to Ca2+, as well as a large catalytic domain. When stimulated by inflammatory factors, activated cytosolic phosphatase A2 (CPLA2) stimulated membrane phospholipid release of arachidonic acid (AA). At this point, the precursor compound AA will eventually produce leukotrienes (LTs) via the 5-LOX pathway. LTs is an important inflammatory mediator involved in many diseases such as atherosclerosis, cardiovascular disease, heart disease and other pathophysiological processes.

Agonist of 5-lipoxygenase

The catalytic activity of 5-LOX was regulated by a variety of substances, including Ca2+, adenosine triphosphate (ATP) FLAP and kinase, which could effectively improve the catalytic activity of 5-LOX. In addition, FLAP is essential for activating 5-LOX. FLAP is a 5-LOX activating protein, which mainly exists in the endoplasmic omentum or nuclear membrane, and its molecular weight is 18 KD. When the cell was activated, the intracellular Ca2+ concentration began to increase, then 5-LOX changed its position in the cell and then combined with the small molecular membrane protein FLAP to play a catalytic role.

5-lipoxygenase and Diseases

It was found that 5-LOX was overexpressed in many kinds of cancer cells, such as prostate cancer, oral cancer, colon cancer and bladder cancer, and the metabolites of 5-LOX pathway, such as leukotriene B4 (LTB4), were detected in these cancer cells. Therefore, researchers have been exploring 5-LOX as a target to develop 5-LOX inhibitors to achieve clinical efficacy in the treatment of cancer and other diseases. The relationship between 5-LOX pathway and tumor is a new research field. Through which mechanism does 5-LOX induce apoptosis? What kind of signals do you rely on to make the 5-LOX approach complete? These problems are worth exploring in depth.

Reference:

Huang Kai, Jiang Shiyun, et al. Q. (2014). 5-Lipoxygenase and its Inhibitors. Chinese Journal of Biochemistry and Molecular Biology. 30(12);1190 -1196