ML346 Chemical Properties

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

ML346 Usage And Synthesis

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

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

ML346(100872-83-1)Related Product Information

• 5-[(4-Nitrobenzoyl)oxy]-2-[(2-pyrimidinylthio)methyl]-4H-pyran-4-one
• ML-228
• ML188 (Racemate)
• ML 18
• ML-098
• ML277
• ML 204
• ML329
• ML364
• VU0456810
• ML188
• ML418
• [4-[Bis(4-chlorophenyl)methyl]piperazin-1-yl]-(5-methyl-4-nitro-1,2-oxazol-3-yl)methanone
• ML213
• N-(3,4-difluorophenyl)-2-pyridin-4-ylquinazolin-4-amine
• ML-327
• PTP1B-IN-2
• ML264