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Submit ReviewVX 745
Description: Potent and selective p38α inhibitor
Alternative Names: VX745,VX-745,Neflamapimod
Chemical Name: 5-(2,6-Dichlorophenyl)-2-[2,4-difluorophenyl)thio]-6H-pyrimido[1,6-b]pyridazin-6-one
Purity: ≥98% (HPLC)
Biological Activity for VX 745
VX 745 is a highly potent and selective p38α/MAPK14 inhibitor, also inhibits p38β (IC50 values are 10 nM and 220 nM respectively). VX 745 blocks TNFα production in LPS-stimulated HWB in vitro (IC50 = 51-180 nM). Also reduces phosphorylation of p38MAPKα and the downstream target Hsp27, leading to vasodilation, reduces IL-1β levels and amyloid plaques in cortex and hippocampus and lowers CSF tau levels in vivo.
External Portal Information for VX 745
Chemicalprobes.org is a portal that offers independent guidance on the selection and/or application of small molecules for research. The use of VX 745 is reviewed on the chemical probes website.
Compound Libraries for VX 745
VX 745 is also offered as part of the Tocriscreen 2.0 Max, Tocriscreen Kinase Inhibitor Library and Tocriscreen Antiviral Library. Find out more about compound libraries available from Tocris.
Technical Data for VX 745
| M. Wt | 436.26 |
| Formula | C19H9Cl2F2N3OS |
| Storage | Store at -20°C |
| Purity | ≥98% (HPLC) |
| CAS Number | 209410-46-8 |
| PubChem ID | 3038525 |
| InChI Key | VEPKQEUBKLEPRA-UHFFFAOYSA-N |
| Smiles | O=C2N=CN1N=C(SC4=CC=C(F)C=C4F)C=CC1=C2C3=C(Cl)C=CC=C3Cl |
The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.
Solubility Data for VX 745
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 43.63 | 100 |
Preparing Stock Solutions for VX 745
The following data is based on the product molecular weight 436.26. Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 2.29 mL | 11.46 mL | 22.92 mL |
| 5 mM | 0.46 mL | 2.29 mL | 4.58 mL |
| 10 mM | 0.23 mL | 1.15 mL | 2.29 mL |
| 50 mM | 0.05 mL | 0.23 mL | 0.46 mL |
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Product Datasheets for VX 745
References for VX 745
References are publications that support the biological activity of the product.
Bagley et al (2007) Rapid synthesis of VX-745: p38 MAP kinase inhibition in Werner syndrome cells. Bioorg.Med.Chem.Lett. 17 5107 PMID: 17659871
Goldstein et al (2010) Selective p38alpha inhibitors clinically evaluated for the treatment of chronic inflammatory disorders. J.Med.Chem. 53 2345 PMID: 19950901
Duffy et al (2011) The discovery of VX-745: a novel and selective p38α kinase inhibitor. ACS Med.Chem.Lett. 2 758 PMID: 24900264
Pandey et al (2022) Neflamapimod induces vasodilation in resistance mesenteric arteries by inhibiting p38 MAPKα and downstream Hsp27 phosphorylation. Sci.Rep. 12 4905 PMID: 35318382
Petrova et al (2020) p38 MAPK signalling regulates cytokine production in IL-33 stimulated type 2 innate lymphoid cells. Sci.Rep. 10 3479 PMID: 32103032
Alam (2015) Selective brain-targeted antagonism of p38 MAPKα reduces hippocampal IL-1 levels and improves Morris Water Maze performance in aged rats. J.Alzheimers Dis. 48 219 PMID: 26401942
If you know of a relevant reference for VX 745, please let us know.
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Keywords: VX 745, VX 745 supplier, VX745, p38a, p38alpha, p38α, MAPK14, inhibitors, inhibits, selective, potent, neflamapimod, neurodegeneration, neuroregeneration, vasodilation, amyloid, tau, TNFalpha, TNFα, VX-745, Neflamapimod, p38, 3915, Tocris Bioscience
5 Citations for VX 745
Citations are publications that use Tocris products. Selected citations for VX 745 include:
Crozier et al (2023) CDK4/6 inhibitor-mediated cell overgrowth triggers osmotic and replication stress to promote senescence. Mol.Cell 83 4062 PMID: 37977118
Ignacio et al (2020) CDK8 Fine-Tunes IL-6 Transcriptional Activities by Limiting STAT3 Resident Time at the Gene Loci. Cell Rep 33 108545 PMID: 33357429
Gerald R et al (2021) Increased ACTL6A occupancy within mSWI/SNF chromatin remodelers drives human squamous cell carcinoma. Mol Cell 81 4964-4978.e8 PMID: 34687603
Singh et al (2018) Differential effect of p38 and MK2 kinase inhibitors on the inflammatory and toxicity biomarkers in vitro. Hum Exp Toxicol 37 521 PMID: 28629242
Haas et al (2013) The inflammatory kinase MAP4K4 promotes reactivation of Kaposi's sarcoma herpesvirus and enhances the invasiveness of infected endothelial cells. PLoS Pathog 9 e1003737 PMID: 24244164
Do you know of a great paper that uses VX 745 from Tocris? Please let us know.
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Literature in this Area
Tocris offers the following scientific literature in this area to showcase our products. We invite you to request* your copy today!
*Please note that Tocris will only send literature to established scientific business / institute addresses.
MAPK Signaling Scientific Review
MAP kinase signaling is integral to the regulation of numerous cellular processes such as proliferation and differentiation, and as a result is an important focus of cancer and immunology research. Updated for 2016, this review discusses the regulation of the MAPK pathway and properties of MAPK cascades. Compounds available from Tocris are listed.
Pathways for VX 745
