[4-(2-pyridinyl)-1-piperazinyl]-(3,4,5-trimethoxyphenyl)methanone, also known as **GSK-3β inhibitor VIII** or **Compound VIII**, is a **small-molecule inhibitor** of **glycogen synthase kinase-3 beta (GSK-3β)**.
**GSK-3β** is a serine/threonine protein kinase that plays a crucial role in various cellular processes, including:
* **Glycogen metabolism:** GSK-3β inhibits glycogen synthase, the enzyme responsible for glycogen synthesis.
* **Cell growth and proliferation:** GSK-3β regulates cell cycle progression and apoptosis.
* **Inflammation and immune response:** GSK-3β is involved in the signaling pathways of various inflammatory cytokines.
* **Neurogenesis and neuronal survival:** GSK-3β plays a role in synaptic plasticity and neuronal survival.
**Compound VIII** is a potent and selective inhibitor of GSK-3β, meaning it binds to and blocks the activity of GSK-3β with high affinity and without significantly affecting other kinases.
**Research Importance:**
**1. Drug Discovery:** Compound VIII has shown promising therapeutic potential in preclinical studies for various diseases related to GSK-3β dysregulation, including:
* **Alzheimer's disease:** GSK-3β inhibition may protect neurons from amyloid-beta toxicity and promote neurogenesis.
* **Type 2 diabetes:** GSK-3β inhibition may improve insulin sensitivity and glucose metabolism.
* **Cancer:** GSK-3β inhibition may inhibit tumor growth and metastasis.
* **Inflammation:** GSK-3β inhibition may reduce inflammation and its associated symptoms.
**2. Understanding GSK-3β Function:** Compound VIII has been used as a valuable tool to study the role of GSK-3β in different cellular processes and disease models. It allows researchers to understand the downstream effects of GSK-3β inhibition and identify new potential drug targets.
**3. Chemical Biology:** Compound VIII has also been studied for its chemical properties and its interaction with GSK-3β, which provides insights into the structure-activity relationships of GSK-3β inhibitors and the design of novel therapeutics.
**Overall, [4-(2-pyridinyl)-1-piperazinyl]-(3,4,5-trimethoxyphenyl)methanone is a valuable research tool with potential therapeutic applications in various diseases associated with GSK-3β dysregulation.**
| ID Source | ID |
|---|---|
| PubMed CID | 28761 |
| CHEMBL ID | 1404540 |
| CHEBI ID | 94210 |
| Synonym |
|---|
| OPREA1_017055 |
| OPREA1_374133 |
| EU-0099612 |
| brn 1601185 |
| 1-(3,4,5-trimethoxybenzoyl)-4-(2-pyridyl)piperazine |
| ketone, 4-(2-pyridyl)piperazinyl 3,4,5-trimethoxyphenyl |
| piperazine, 1-(2-pyridyl)-4-(3,4,5-trimethoxybenzoyl)- |
| 4-(2-pyridyl)piperazinyl 3,4,5-trimethoxyphenyl ketone |
| (4-pyridin-2-yl-piperazin-1-yl)-(3,4,5-trimethoxy-phenyl)-methanone |
| smr000518691 |
| MLS001210948 , |
| BRD-K84102257-001-05-7 |
| AKOS000643532 |
| (4-pyridin-2-ylpiperazin-1-yl)-(3,4,5-trimethoxyphenyl)methanone |
| NCGC00245374-01 |
| 17766-77-7 |
| 5-23-03-00029 (beilstein handbook reference) |
| BRD-K84102257-001-08-1 |
| HMS2816L14 |
| AB00110443-01 |
| cid_28761 |
| [4-(2-pyridinyl)-1-piperazinyl]-(3,4,5-trimethoxyphenyl)methanone |
| bdbm69691 |
| [4-(2-pyridyl)piperazino]-(3,4,5-trimethoxyphenyl)methanone |
| CHEMBL1404540 |
| DTXSID10170364 |
| VU0151509-1 |
| sr-01000594870 |
| SR-01000594870-1 |
| CHEBI:94210 |
| Q27165981 |
| Class | Description |
|---|---|
| pyridines | Any organonitrogen heterocyclic compound based on a pyridine skeleton and its substituted derivatives. |
| piperazines | |
| [compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Protein | Taxonomy | Measurement | Average (µ) | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Chain A, MAJOR APURINIC/APYRIMIDINIC ENDONUCLEASE | Homo sapiens (human) | Potency | 0.0168 | 0.0032 | 45.4673 | 12,589.2998 | AID2517 |
| nonstructural protein 1 | Influenza A virus (A/WSN/1933(H1N1)) | Potency | 19.9526 | 0.2818 | 9.7212 | 35.4813 | AID2326 |
| 67.9K protein | Vaccinia virus | Potency | 5.0119 | 0.0001 | 8.4406 | 100.0000 | AID720579 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| glycogen synthase kinase-3 beta isoform 1 | Homo sapiens (human) | EC50 (µMol) | 45.9000 | 0.2125 | 22.1562 | 83.9400 | AID434954 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Cyclin-dependent kinase 5, regulatory subunit 1 (p35) | Homo sapiens (human) | AC50 | 2.7530 | 0.0100 | 9.0955 | 33.0300 | AID504545 |
| CDK5 | Homo sapiens (human) | AC50 | 2.7530 | 0.0100 | 9.0955 | 33.0300 | AID504545 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID588501 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set | 2010 | Current protocols in cytometry, Oct, Volume: Chapter 13 | Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening. |
| AID588501 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set | 2006 | Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5 | Microsphere-based protease assays and screening application for lethal factor and factor Xa. |
| AID588501 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set | 2010 | Assay and drug development technologies, Feb, Volume: 8, Issue:1 | High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors. |
| AID504812 | Inverse Agonists of the Thyroid Stimulating Hormone Receptor: HTS campaign | 2010 | Endocrinology, Jul, Volume: 151, Issue:7 | A small molecule inverse agonist for the human thyroid-stimulating hormone receptor. |
| AID504810 | Antagonists of the Thyroid Stimulating Hormone Receptor: HTS campaign | 2010 | Endocrinology, Jul, Volume: 151, Issue:7 | A small molecule inverse agonist for the human thyroid-stimulating hormone receptor. |
| AID588497 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set | 2010 | Current protocols in cytometry, Oct, Volume: Chapter 13 | Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening. |
| AID588497 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set | 2006 | Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5 | Microsphere-based protease assays and screening application for lethal factor and factor Xa. |
| AID588497 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set | 2010 | Assay and drug development technologies, Feb, Volume: 8, Issue:1 | High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors. |
| AID651635 | Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression | |||
| AID588499 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set | 2010 | Current protocols in cytometry, Oct, Volume: Chapter 13 | Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening. |
| AID588499 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set | 2006 | Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5 | Microsphere-based protease assays and screening application for lethal factor and factor Xa. |
| AID588499 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set | 2010 | Assay and drug development technologies, Feb, Volume: 8, Issue:1 | High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors. |
| AID1745845 | Primary qHTS for Inhibitors of ATXN expression | |||
| AID1794808 | Fluorescence-based screening to identify small molecule inhibitors of Plasmodium falciparum apicoplast DNA polymerase (Pf-apPOL). | 2014 | Journal of biomolecular screening, Jul, Volume: 19, Issue:6 | A High-Throughput Assay to Identify Inhibitors of the Apicoplast DNA Polymerase from Plasmodium falciparum. |
| AID1794808 | Fluorescence-based screening to identify small molecule inhibitors of Plasmodium falciparum apicoplast DNA polymerase (Pf-apPOL). | |||
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 1 (14.29) | 29.6817 |
| 2010's | 4 (57.14) | 24.3611 |
| 2020's | 2 (28.57) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be weak demand-to-supply ratio for research on this compound.
| This Compound (12.22) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 0 (0.00%) | 5.53% |
| Reviews | 0 (0.00%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 7 (100.00%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||