For research use only. Not for therapeutic Use.
APY-0201 (Cat.No:I000914), also known as AMG-0201, is a potent and selective inhibitor of the protein kinase PKR-like endoplasmic reticulum kinase (PERK). It is currently being investigated as a potential treatment for various types of cancer and neurodegenerative diseases. APY-0201 has shown promising results in preclinical studies, and clinical trials are ongoing.
| Catalog Number | I000914 |
| CAS Number | 1232221-74-7 |
| Molecular Formula | C₂₃H₂₃N₇O |
| Purity | ≥95% |
| Target | IL-12/23 inhibitor |
| Solubility | DMSO: ≥ 35 mg/mL |
| Storage | Store at -20°C |
| IC50 | 5.2 nM [1] |
| IUPAC Name | N-[(E)-(3-methylphenyl)methylideneamino]-7-morpholin-4-yl-2-pyridin-4-ylpyrazolo[1,5-a]pyrimidin-5-amine |
| InChI | InChI=1S/C23H23N7O/c1-17-3-2-4-18(13-17)16-25-27-21-15-2 |
| InChIKey | RFZQYGBLRIKROZ-XYGWBWBKSA-N |
| SMILES | CC1=CC=CC(=C1)C=NNC2=NC3=CC(=NN3C(=C2)N4CCOCC4)C5=CC=NC=C5 |
| Reference | 1:Bioorg Med Chem. 2014 Jun 1;22(11):3021-9. doi: 10.1016/j.bmc.2014.03.036. Epub 2014 Apr 13. Structure-activity relationship study, target identification, and pharmacological characterization of a small molecular IL-12/23 inhibitor, APY0201.Hayakawa N,Noguchi M,Takeshita S,Eviryanti A,Seki Y,Nishio H,Yokoyama R,Noguchi M,Shuto M,Shima Y,Kuribayashi K,Kageyama S,Eda H,Suzuki M,Hatta T,Iemura S,Natsume T,Tanabe I,Nakagawa R,Shiozaki M,Sakurai K,Shoji M,Andou A,Yamamoto T, PMID: 24767819 DOI: 10.1016/j.bmc.2014.03.036 </br><span>Abstract:</span> Interleukin-12 (IL-12) and IL-23 are proinflammatory cytokines and therapeutic targets for inflammatory and autoimmune diseases, including inflammatory bowel diseases, psoriasis, rheumatoid arthritis, and multiple sclerosis. We describe the discovery of APY0201, a unique small molecular IL-12/23 production inhibitor, from activated macrophages and monocytes, and demonstrate ameliorated inflammation in an experimental model of colitis. Through a chemical proteomics approach using a highly sensitive direct nanoflow LC-MS/MS system and bait compounds equipped with the FLAG epitope associated regulator of PIKfyve (ArPIKfyve) was detected. Further study identified its associated protein phosphoinositide kinase, FYVE finger-containing (PIKfyve), as the target protein of APY0201, which was characterized as a potent, highly selective, ATP-competitive PIKfyve inhibitor that interrupts the conversion of phosphatidylinositol 3-phosphate (PtdIns3P) to PtdIns(3,5)P2. These results elucidate the function of PIKfyve kinase in the IL-12/23 production pathway and in IL-12/23-driven inflammatory disease pathologies to provide a compelling rationale for targeting PIKfyve kinase in inflammatory and autoimmune diseases. Copyright © 2014 Elsevier Ltd. All rights reserved. |
