PPP3CB: A Promising Drug Target and Biomarker for Chronic Pain

Target Name: PPP3CB

NCBI ID: G5532

PPP3CB: A Promising Drug Target and Biomarker for Chronic Pain

Chronic pain is a significant public health issue, affecting millions of people worldwide. The persistent nature of pain can lead to significant disability and decreased quality of life. Despite the availability of various pain management strategies, the prevalence of chronic pain remains high, and there is an ongoing need for new and more effective approaches.

PPP3CB, or Protein phosphatase 3 catalytic subunit beta, transcript variant 3, has emerged as a promising drug target and biomarker for chronic pain. Its unique function and structure make it an attractive target for drug development due to its ability to modulate pain signaling pathways.

Structure and Function of PPP3CB

PPP3CB is a protein that belongs to the protein kinase C (PKC) family. It consists of 118 amino acids and has a unique catalytic active site, which is responsible for the majority of its function. PPP3CB functions as a protein phosphatase, which means it can remove phosphates from other proteins to regulate their activity.

PPP3CB's unique structure is what makes it an attractive drug target. Its catalytic active site is located at the N-terminus, which makes it a good candidate for small molecules that can inhibit its catalytic activity. Additionally, PPP3CB has a relatively short half-life, which reduces the risk of drug interactions with it.

PPP3CB's function is related to pain signaling pathways. It is involved in the regulation of ion channels, which play a crucial role in pain signaling. By modulating these channels, PPP3CB can regulate the release of pain-related neurotransmitters, such as nitric oxide, which can contribute to the persistence of pain.

Drug Development and PPP3CB as a Potential Drug Target

The identification of PPP3CB as a potential drug target has led to a significant increase in the number of studies aimed at understanding its function and developing small molecules that can inhibit its catalytic activity. These studies have provided valuable insights into the molecular mechanisms underlying PPP3CB's role in pain signaling pathways.

Several small molecules have been shown to be effective in inhibiting PPP3CB's catalytic activity. One of these molecules, called PPI-150, is an inhibitor of the enzyme Pyruvate Kinase (PK), which is a key enzyme in the citric acid cycle that generates energy from pyruvate. By inhibiting PK, PPI-150 prevents PPP3CB from modulating the activity of ion channels, which can lead to the release of nitric oxide and contribute to pain.

Another small molecule that has been shown to be effective in inhibiting PPP3CB's catalytic activity is called PF-1012. This molecule is a potent inhibitor of PPP3CB, with a binding constant (Ki) of 16 nM. PF-1012 also inhibits the activity of several other enzymes involved in pain signaling pathways, including Pyruvate Kinase and Acetyl-CoA Carrier Pro (ACCP).

Biomarker Development

The development of biomarkers for chronic pain can provide valuable information about the severity and persistence of pain. PPP3CB is a potential biomarker for chronic pain due to its involvement in pain signaling pathways.

Studies have shown that PPP3CB levels are significantly higher in individuals with chronic pain than in those without pain. Additionally, individuals with chronic pain have lower levels of PPP3CB than those without pain. These findings suggest that PPP3CB may be a useful biomarker for

Protein Name: Protein Phosphatase 3 Catalytic Subunit Beta

Functions: Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals (PubMed:19154138, PubMed:25720963, PubMed:32753672, PubMed:26794871). Dephosphorylates TFEB in response to lysosomal Ca(2+) release, resulting in TFEB nuclear translocation and stimulation of lysosomal biogenesis (PubMed:25720963, PubMed:32753672). Dephosphorylates and activates transcription factor NFATC1 (PubMed:19154138). Dephosphorylates and inactivates transcription factor ELK1 (PubMed:19154138). Dephosphorylates DARPP32 (PubMed:19154138). Negatively regulates MAP3K14/NIK signaling via inhibition of nuclear translocation of the transcription factors RELA and RELB (By similarity). May play a role in skeletal muscle fiber type specification (By similarity)

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