Study on Prolyl 4-Hydroxylase as A Drug Target and Biomarker in Cancer

Target Name: Prolyl 4-hydroxylase

NCBI ID: P36692

Prolyl 4-hydroxylase

Other Name(s): 4-PH | Procollagen-proline,2-oxoglutarate-4-dioxygenase

Study on Prolyl 4-Hydroxylase as A Drug Target and Biomarker in Cancer

Prolyl 4-hydroxylase (4-PH) is an enzyme that plays a crucial role in the regulation of protein structure and function. It is a key enzyme in the protein folding process and is responsible for many important biological processes within cells. biological processes, such as cell division, cell growth, cell apoptosis, etc. In human diseases, the abnormal activity of 4-PH may lead to a variety of diseases. Therefore, studying the role and intervention strategies of 4-PH in diseases has important theoretical and practical value.

4-PH is a single-stranded DNA-binding enzyme that catalyzes the reaction between the hydroxyl groups on DNA and the amide groups of proteins to form disulfide bonds. During the protein folding process, 4-PH gives the protein the desired shape by forming stable 伪-helices and 尾-sheets in the protein's secondary structure. In addition, 4-PH can also play a role in protein phosphorylation processes, such as in the insulin signaling pathway.

The activity of 4-PH is affected by many factors, including substrate concentration, temperature, pH value and inhibitors. Under physiological conditions, the activity of 4-PH is usually between 20-70掳C, while under pathological conditions its activity may be altered. For example, in tumor cells, the activity of 4-PH is often elevated, which may be due to increased metabolic activity of tumor cells and increased intracellular production of 4-PH.

There are differences in 4-PH activity in tumor cells compared with normal cells. Studies have shown that the activity of 4-PH in tumor cells is often 10 to 100 times higher than that in normal cells. This difference opens up the possibility of using 4-PH as a drug target or biomarker. By inhibiting the activity of 4-PH, the growth of tumor cells can be slowed down and even the invasion of tumor cells can be prevented.

At present, research on 4-PH mainly focuses on the following aspects:

1. Research on 4-PH as a drug target

The discovery of a highly active state of 4-PH in tumor cells makes 4-PH an attractive drug target. Much research has been devoted to finding compounds capable of inhibiting the activity of 4-PH. These compounds can be divided into the following categories:

(1) HSP90 mimic: HSP90 is a protein binding partner that can bind to 4-PH, thereby inhibiting the activity of 4-PH. HSP90 mimetics can be administered orally or intravenously and have good bioavailability and safety.

(2) Disulfide alkyl compounds: These compounds can simulate the structure of disulfide bonds, bind to 4-PH and inhibit its activity. For example, disulfide fatty acids and amine disulfides can significantly inhibit the activity of 4-PH.

(3) Phosphorylation inhibitors: Phosphorylation is an important component of 4-PH activity. Therefore, phosphorylation inhibitors can inhibit the phosphorylation of 4-PH, thereby inhibiting its activity. These compounds include sodium dihydrogen phosphate, phosphoric acid hydrochloric acid, and phosphoenolmalonic acid, among others.

2. Research on 4-PH as a biological marker

The highly active state of 4-PH in tumor cells makes it a potential tumor biomarker. Some studies have attempted to diagnose tumors by detecting 4-PH activity. For example, Western blotting is a widely used method to detect tumor biomarkers. By using specific antibodies, the activity of 4-PH can be detected and used for tumor diagnosis and monitoring.

In addition, some studies have also explored the possibility of using 4-PH as a target for tumor treatment. By inhibiting the activity of 4-PH, the growth of tumor cells can be slowed down and even the invasion of tumor cells can be prevented. For example, some studies are exploring the use of 4-PH inhibitors to treat tumors.

3. The mechanism of action of 4-PH in tumor cells

The mechanism of action of 4-PH in tumor cells is unclear, but studies have shown that the activity of 4-PH may be involved in processes such as tumor cell growth, apoptosis, and angiogenesis.

Protein Name: Prolyl 4-hydroxylase

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