HSD17B8: A Potential Drug Target for Psychiatric Disorders (G7923)

Target Name: HSD17B8

NCBI ID: G7923

HSD17B8: A Potential Drug Target for Psychiatric Disorders

HSD17B8, also known as 17-beta-hydroxysteroid dehydrogenase 8, is a gene that encodes a protein involved in the synthesis and metabolism of various steroids in the body. One of the primary functions of this protein is to convert androgen, which is a male sex hormone, into 17-beta-hydroxysteroid, which is a more potent and potent aromatizing steroid. In this article, we will discuss HSD17B8 as a drug target and its potential uses in the treatment of various diseases.

HSD17B8 gene function and localization

The HSD17B8 gene is located on chromosome 17, specifically on the q21 region. It encodes a protein that spans 1,942 amino acids and has a calculated molecular weight of 24.9 kDa. The protein has a characteristic alpha-helices structure and is localized to the cytoplasm.

Expression of HSD17B8 protein

HSD17B8 is a widely expressed gene in various tissues, including the brain, heart, liver, and pancreas. The protein is mainly expressed in the liver and pancreas, with lower levels of expression in the heart and brain. The protein is also known to be expressed in various tissues and organs, including the placenta, fetal brain, and fetal heart.

Drug targeting and applications

HSD17B8 has been identified as a potential drug target due to its involvement in the synthesis and metabolism of various steroids. Many studies have shown that inhibitors of HSD17B8 can decrease the production of androgens in various tissues, including the brain, which is known to play a crucial role in the development and progression of various psychiatric and neurological disorders.

One of the most promising strategies for targeting HSD17B8 is the use of small molecules, such as inhibitors or modulators, that can inhibit the activity of the protein. Many of these molecules have been shown to be effective in preclinical studies and have been tested in clinical trials. For example, a small molecule inhibitor, called R172-826, has been shown to decrease the production of androgens in various tissues, including the brain, while another small molecule modulator, called 17-beta-D-hydroxy-steroid dehydrogenase 8 modulator (HSD17B8-mod), has been shown to decrease the production of androgens in the liver.

Another approach to targeting HSD17B8 is the use of antibodies that can specifically bind to the protein and prevent it from functioning. Many studies have shown that antibodies against HSD17B8 have been effective in preclinical studies and have been tested in clinical trials. For example, a monoclonal antibody (mAb) called 17-beta-D-hydroxy-steroid dehydrogenase 8 antibody has been shown to effectively block the production of androgens in various tissues, including the brain.

Clinical applications

HSD17B8 has the potential to be a useful drug target for the treatment of various psychiatric and neurological disorders, including depression, anxiety, and neurodegenerative diseases. Many studies have shown that inhibitors or modulators of HSD17B8 have the potential to treat these disorders by reducing the production of androgens.

For example, a small molecule inhibitor, called R172-826, has been shown to decrease the production of androgens in various tissues, including the brain, while another small molecule modulator, called 17-beta-D-hydroxy-steroid dehydrogenase 8 modulator (HSD17B8-mod), has been shown to decrease the production of androgens in the liver. Preclinical studies have also shown that these molecules have the potential to treat

Protein Name: Hydroxysteroid 17-beta Dehydrogenase 8

Functions: Required for the solubility and assembly of the heterotetramer 3-ketoacyl-[acyl carrier protein] (ACP) reductase functional complex (KAR or KAR1) that forms part of the mitochondrial fatty acid synthase (mtFAS). Alpha-subunit of the KAR complex that acts as a scaffold protein required for the stability of carbonyl reductase type-4 (CBR4, beta-subunit of the KAR complex) and for its 3-ketoacyl-ACP reductase activity, thereby participating in mitochondrial fatty acid biosynthesis. Catalyzes the NAD-dependent conversion of (3R)-3-hydroxyacyl-CoA into 3-ketoacyl-CoA (3-oxoacyl-CoA) with no chain length preference; this enzymatic activity is not needed for the KAR function (PubMed:19571038, PubMed:25203508, PubMed:30508570). Prefers (3R)-3-hydroxyacyl-CoA over (3S)-3-hydroxyacyl-CoA and displays enzymatic activity only in the presence of NAD(+) (PubMed:19571038). Cooperates with enoyl-CoA hydratase 1 in mitochondria, together they constitute an alternative route to the auxiliary enzyme pathways for the breakdown of Z-PUFA (cis polyunsaturated fatty acid) enoyl-esters (Probable) (PubMed:30508570). NAD-dependent 17-beta-hydroxysteroid dehydrogenase with highest activity towards estradiol (17beta-estradiol or E2). Has very low activity towards testosterone and dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one). Primarily an oxidative enzyme, it can switch to a reductive mode determined in the appropriate physiologic milieu and catalyze the reduction of estrone (E1) to form biologically active 17beta-estradiol (PubMed:17978863)

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