VPS34 inhibitor 1
Solid powder
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VPS34 inhibitor 1 is a small molecule inhibitor that targets the class III phosphatidylinositol 3-kinase (PI3K) VPS34. It has gained significant attention in recent years due to its potential therapeutic applications in various diseases, including cancer, neurodegenerative disorders, and infectious diseases. This paper aims to provide a comprehensive review of VPS34 inhibitor 1, including its method of synthesis or extraction, chemical structure and biological activity, biological effects, applications, future perspectives, and challenges.
391.479
391.479
Formulation:
391.479
Source:
Usage:
VPS34 inhibitor 1
The product is for non-human research only. Not for therapeutic or veterinary use.
Catalog Number: BT-254312
CAS Number: 1383716-46-8
Molecular Formula: C21H25N7O
Molecular Weight: 391.479
Purity: ≥ 99%
Inventory: In Stock
| Size | SKU | Price | |
|---|---|---|---|
| 1mg | bt-254312-1mg | $295.85 |
| CAS Number | 1383716-46-8 |
|---|---|
| Product Name | VPS34 inhibitor 1 |
| Molecular Formula | C21H25N7O |
| Molecular Weight | 391.479 |
| Appearance | Solid powder |
| InChI | InChI=1S/C21H25N7O/c1-21(2,29)13-25-19-24-12-16(18(28-19)11-14-3-4-14)17-7-10-23-20(27-17)26-15-5-8-22-9-6-15/h5-10,12,14,29H,3-4,11,13H2,1-2H3,(H,24,25,28)(H,22,23,26,27) |
| InChI Key | XJTIGGCBXFIZJV-UHFFFAOYSA-N |
| IUPAC Name | 1-[[4-(cyclopropylmethyl)-5-[2-(pyridin-4-ylamino)pyrimidin-4-yl]pyrimidin-2-yl]amino]-2-methylpropan-2-ol |
| Description | VPS34 inhibitor 1 is a small molecule inhibitor that targets the class III phosphatidylinositol 3-kinase (PI3K) VPS34. It has gained significant attention in recent years due to its potential therapeutic applications in various diseases, including cancer, neurodegenerative disorders, and infectious diseases. This paper aims to provide a comprehensive review of VPS34 inhibitor 1, including its method of synthesis or extraction, chemical structure and biological activity, biological effects, applications, future perspectives, and challenges. |
| Method of Synthesis or Extraction | VPS34 inhibitor 1 can be synthesized using various methods, including chemical synthesis and extraction from natural sources. Chemical synthesis involves the use of organic chemistry techniques to create the compound from scratch. On the other hand, extraction involves isolating the compound from natural sources, such as plants or microorganisms. Efficiency and yield of each method vary depending on the specific conditions used. Chemical synthesis can provide high yields and purity, but it can be time-consuming and expensive. Extraction, on the other hand, can be more cost-effective, but the yield and purity of the compound can be lower. Environmental and safety considerations are also important factors to consider when choosing a method of synthesis or extraction. Chemical synthesis can produce hazardous waste and require the use of toxic chemicals, while extraction can have a lower environmental impact but may require the use of organic solvents. |
| Chemical Structure and Biological Activity | VPS34 inhibitor 1 has a chemical structure that consists of a pyrimidine core with a substituted phenyl group and a pyridine ring. It is a potent and selective inhibitor of VPS34, which is involved in autophagy, a cellular process that degrades damaged or unwanted cellular components. The mechanism of action of VPS34 inhibitor 1 involves binding to the ATP-binding site of VPS34, inhibiting its activity and preventing the formation of autophagosomes. This leads to the accumulation of damaged cellular components and ultimately induces cell death. |
| Biological Effects | VPS34 inhibitor 1 has been shown to have various biological effects on cell function and signal transduction. It has been demonstrated to induce autophagy-dependent cell death in cancer cells and inhibit the replication of certain viruses, such as Zika and Dengue viruses. Potential therapeutic and toxic effects of VPS34 inhibitor 1 are still being investigated. It has been suggested that VPS34 inhibitor 1 may have therapeutic potential in cancer, neurodegenerative disorders, and infectious diseases. However, it may also have toxic effects on normal cells and tissues, which need to be further studied. |
| Applications | VPS34 inhibitor 1 has various applications in medical, environmental, and industrial research. In medical research, it has been studied for its role in drug development, and several clinical trials are currently underway to investigate its potential therapeutic effects in cancer and other diseases. In environmental research, VPS34 inhibitor 1 has been studied for its effects on ecosystems and its potential role in pollution management. It has been shown to have potential as a sustainable and environmentally friendly alternative to traditional chemical pesticides. In industrial research, VPS34 inhibitor 1 has been used in manufacturing processes to improve product quality and efficiency. Health and safety considerations are important when using VPS34 inhibitor 1 in industrial settings, as it may have toxic effects on workers and the environment. |
| Future Perspectives and Challenges | Current limitations in the use and study of VPS34 inhibitor 1 include its potential toxicity and the need for further research to fully understand its biological effects and therapeutic potential. Possible solutions and improvements include the development of more selective and less toxic inhibitors and the use of advanced techniques, such as CRISPR-Cas9, to study its biological effects. Future trends and prospects in the application of VPS34 inhibitor 1 in scientific research include its potential use in combination therapies for cancer and other diseases and its role in understanding the mechanisms of autophagy and other cellular processes. Conclusion In conclusion, VPS34 inhibitor 1 is a promising small molecule inhibitor with potential therapeutic applications in various diseases. Its method of synthesis or extraction, chemical structure and biological activity, biological effects, applications, future perspectives, and challenges have been discussed in this paper. Further research is needed to fully understand its potential and limitations and to develop safer and more effective inhibitors. |
| SMILES | CC(C)(CNC1=NC=C(C(=N1)CC2CC2)C3=NC(=NC=C3)NC4=CC=NC=C4)O |
| Synonyms | VPS34 inhibitor 1;VPS34-IN1 |
| Reference | 1. Biochem J. 2014 Nov 1;463(3):413-27. doi: 10.1042/BJ20140889. Characterization of VPS34-IN1, a selective inhibitor of Vps34, reveals that the phosphatidylinositol 3-phosphate-binding SGK3 protein kinase is a downstream target of class III phosphoinositide 3-kinase. Bago R(1), Malik N(1), Munson MJ(1), Prescott AR(2), Davies P(1), Sommer E(1), Shpiro N(1), Ward R(3), Cross D(3), Ganley IG(1), Alessi DR(1). Author information: (1)*MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K. (2)†Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K. (3)‡Oncology iMED, AstraZeneca, Alderley Park, Cheshire SK10 4TG, U.K. The Vps34 (vacuolar protein sorting 34) class III PI3K (phosphoinositide 3-kinase) phosphorylates PtdIns (phosphatidylinositol) at endosomal membranes to generate PtdIns(3)P that regulates membrane trafficking processes via its ability to recruit a subset of proteins possessing PtdIns(3)P-binding PX (phox homology) and FYVE domains. In the present study, we describe a highly selective and potent inhibitor of Vps34, termed VPS34-IN1, that inhibits Vps34 with 25 nM IC50 in vitro, but does not significantly inhibit the activity of 340 protein kinases or 25 lipid kinases tested that include all isoforms of class I as well as class II PI3Ks. Administration of VPS34-IN1 to cells induces a rapid dose-dependent dispersal of a specific PtdIns(3)P-binding probe from endosome membranes, within 1 min, without affecting the ability of class I PI3K to regulate Akt. Moreover, we explored whether SGK3 (serum- and glucocorticoid-regulated kinase-3), the only protein kinase known to interact specifically with PtdIns(3)P via its N-terminal PX domain, might be controlled by Vps34. Mutations disrupting PtdIns(3)P binding ablated SGK3 kinase activity by suppressing phosphorylation of the T-loop [PDK1 (phosphoinositide-dependent kinase 1) site] and hydrophobic motif (mammalian target of rapamycin site) residues. VPS34-IN1 induced a rapid ~50-60% loss of SGK3 phosphorylation within 1 min. VPS34-IN1 did not inhibit activity of the SGK2 isoform that does not possess a PtdIns(3)P-binding PX domain. Furthermore, class I PI3K inhibitors (GDC-0941 and BKM120) that do not inhibit Vps34 suppressed SGK3 activity by ~40%. Combining VPS34-IN1 and GDC-0941 reduced SGK3 activity ~80-90%. These data suggest SGK3 phosphorylation and hence activity is controlled by two pools of PtdIns(3)P. The first is produced through phosphorylation of PtdIns by Vps34 at the endosome. The second is due to the conversion of class I PI3K product, PtdIns(3,4,5)P3 into PtdIns(3)P, via the sequential actions of the PtdIns 5-phosphatases [SHIP1/2 (Src homology 2-domain-containing inositol phosphatase 1/2)] and PtdIns 4-phosphatase [INPP4B (inositol polyphosphate 4-phosphatase type II)]. VPS34-IN1 will be a useful probe to delineate physiological roles of the Vps34. Monitoring SGK3 phosphorylation and activity could be employed as a biomarker of Vps34 activity, in an analogous manner by which Akt is used to probe cellular class I PI3K activity. Combining class I (GDC-0941) and class III (VPS34-IN1) PI3K inhibitors could be used as a strategy to better analyse the roles and regulation of the elusive class II PI3K. |
| PubChem Compound | VPS34 inhibitor 1 |
| Last Modified | May 30 2023 |