| Identification | Back Directory | [Name]
ML346 | [CAS]
100872-83-1 | [Synonyms]
ML346
CS-2056
ML346;ML 346
ML346 - CID 767276
2,4,6(1H,3H,5H)-Pyrimidinetrione, 5-[3-(4-methoxyphenyl)-2-propen-1-ylidene]- | [EINECS(EC#)]
604-604-1 | [Molecular Formula]
C14H12N2O4 | [MOL File]
100872-83-1.mol | [Molecular Weight]
272.26 |
| Chemical Properties | Back Directory | [Melting point ]
266-268 °C(Solv: ethyl acetate (141-78-6)) | [density ]
1.374±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
Soluble in DMSO:8.0(Max Conc. mg/mL);29.38(Max Conc. mM) | [form ]
A crystalline solid | [pka]
7.42±0.20(Predicted) | [color ]
Pink to red |
| Hazard Information | Back Directory | [Description]
ML-346 is an activator of the heat shock response that induces the expression of the heat shock proteins HSP70, HSP40, and HSP27. It induces the expression of the oxidative stress response genes HO1, GCLM, and BiP in mouse embryonic fibroblasts (MEFs) and pretreatment protects cells from severe heat shock-induced death and H2O2-induced apoptosis. It promotes folding of metastable proteins in models of conformational disease, including cellular models of Huntingtin aggregation and cystic fibrosis. It reduces aggregate formation in PC12 cells expressing human Huntingtin exon 1 containing a 74 glutamine expansion when used at a concentration of 10 μM. It also corrects trafficking of cystic fibrosis transmembrane conductance regulator proteins bearing the F508 deletion (ΔF508-CFTR) mutation carried by the majority of cystic fibrosis patients, leading to increased cell surface expression. | [Uses]
ML346 is an activator of Hsp70 expression and HSF-1 activity, with an EC50 of 4.6 μM for Hsp70. ML346 restores protein folding in conformational disease models, without significant cytotoxicity or lack of specificity. ML346 induces specific increases in genes and protein effectors of the heat shock response (HSR), including chaperones such as Hsp70, Hsp40, and Hsp27[1]. | [in vivo]
ML346 suppress the aggregation of polyQ35 in a C. elegans model, suggesting the probe has efficacy in modifying protein aggregation and associated toxicity[1]. | [IC 50]
HSP70: 4.6 μM (EC50, HeLa cells) | [References]
[1] Calamini B, et al. ML346: A Novel Modulator of Proteostasis for Protein Conformational Diseases.Probe Reports from the NIH Molecular Libraries Program. Bethesda (MD): National Center for Biotechnology Information (US); 2010-.
2012 Dec 17. PMID:23833797
[2] Calamini B, et al. Small-molecule proteostasis regulators for protein conformational diseases. Nat Chem Biol. 2011 Dec 25;8(2):185-96. DOI:10.1038/nchembio.763 |
|
|