324521

Eeyarestatin I

A cell-permeable oxo-imidazolidinyl-hydroxyurea that localizes to ER, where it interacts with AAA ATPase p97 via its nitrofuran-containing moiety, without exhibiting affinity toward Hsp70 / ATPase NSF

• Sinônimo(s): Eeyarestatin I, 1-(4-Chloro-phenyl)-3-(3-(4-chloro-phenyl)-5,5-dimethyl-1-(3-(5-nitro-furan-2-yl)-allyldiene-hydrazinocarbonylmethyl)-2-oxo-imidazolidin-4-yl)-1-hydroxyl-urea, EerI, ES1, Valosin-containing Protein Inhibitor II, VCP Inhibitor II, ERAD Inhibitor II, p97 Inhibitor II
• Fórmula empírica (Notação de Hill): C₂₇H₂₅Cl₂N₇O₇
• Número CAS: 412960-54-4
• Peso molecular: 630.44
• Código UNSPSC: 12352200
• NACRES: NA.51

Propriedades

• Nível de qualidade: 100
• Ensaio: ≥90% (HPLC)
• forma: solid
• fabricante/nome comercial: Calbiochem^®
• condição de armazenamento: OK to freeze; protect from light
• cor: light yellow-orange
• solubilidade: DMSO: 100 mg/mL
• Condições de expedição: ambient
• temperatura de armazenamento: 2-8°C
• InChI: 1S/C27H25Cl2N7O7/c1-27(2)24(35(40)25(38)31-19-9-5-17(28)6-10-19)34(20-11-7-18(29)8-12-20)26(39)33(27)16-22(37)32-30-15-3-4-21-13-14-23(43-21)36(41)42/h3-15,24,40H,16H2,1-2H3,(H,31,38)(H,32,37)
• chave InChI: JTUXTPWYZXWOIB-UHFFFAOYSA-N

Descrição

Descrição geral

A cell-permeable oxo-imidazolidinyl-hydroxyurea that preferentially localizes to ER, where it interacts with AAA (ATPase associated with diverse cellular activities) ATPase p97 (K_d = 5 - 10 µM) via its nitrofuran-containing moiety, without exhibiting affinity toward Hsp70 or AAA ATPase NSF (N-methylmaleimide-sensitive factor). Evidence indicates that EerI cellular metabolite, but not EerI itself, is responsible for the inhibition of ER membrane translocon sec61 complex-mediated transfer of newly synthesized polypeptide, resulting in a blockage of ER-mediated posttranslational glycosylation and signal peptide removal (Effective conc. = 8 µM in HepG2 and HeLa cultures). Ether independent or as a consequence of the early effect on sec61 complex, EerI culture treatment also induces a selective dissociation of an 180 kDa protein from the atx3-containing p97/VCP (Valosin-containing protein) complex and a blockage of the complex-associated deubiquitination of ERAD (ER-associated protein degradation) substrates in a reversible manner, resulting in an accumulation of polyubiquitinated proteins (Effective conc. = 10 µM in A9 and 293T cultures). EerI culture treatment (10 µM) is also demonstrated to selectively induce cytotoxicity in lymphoid cell lines, BJAB, HBL-2, JEKO-1, Jurkat, KMS-12, MINO, as well as primary leukemia cells from CLL (chronic lymphocytic leukemia) patients, but not PBMC from healthy donors, by upregulating the BH3-only pro-apoptotic protein NOXA in cancer cells via ATF3/4 activation and a downregulation of H2A ubiquitination. Unlike DBeQ (Cat. No. 506190), EeRI does not inhibit p97 ATPase activity.

A cell-permeable oxo-imidazolidinyl-hydroxyurea whose cellular metabolite is shown to effectively inhibit the ER membrane translocon sec61 complex-mediated transfer of newly synthesized polypeptide, resulting in a blockage of ER-mediated posttranslational glycosylation and signal peptide removal (Effective conc. = 8 µM in HepG2 and HeLa cultures). Ether independent or as a consequence of the early effect on sec61 complex, EerI culture treatment also induces a selective dissociation of an 180 kDa protein from the atx3-containing p97/VCP (Valosin-containing protein) ATPase complex and a blockage of the p97 complex-associated deubiquitination of ERAD (ER-associated protein degradation) substrates in a reversible manner, resulting in an accumulation of polyubiquitinated proteins (Effective conc. = 10 µM in A9 and 293T cultures). EerI culture treatment (10 µM) is also demonstrated to selectively induce cytotoxicity in lymphoid cell lines, BJAB, HBL-2, JEKO-1, Jurkat, KMS-12, MINO, as well as primary leukemia cells from CLL (chronic lymphocytic leukemia) patients, but not PBMC from healthy donors, by upregulating the BH3-only pro-apoptotic protein NOXA in cancer cells via ATF3/4 activation and a downregulation of H2A ubiquitination.

Embalagem

Packaged under inert gas

Advertência

Toxicity: Standard Handling (A)

Reconstituição

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

It is recommended to prepare a stock solution for 3 month use each time and store the unreconstituted material in solid form, protected from moisture and preferably under inert gas, for best long-term stability during storage.

Outras notas

Chou, T.F., et al. 2011. Proc. Natl. Acad. Sci. USA108, 4834.
Wang. Q, et al. 2010. PLoS ONE5, e15479.
Cross, B.C.S., et al. 2009. J. Cell. Sci.122, 4393.
Wang, Q., et al. 2009. Proc. Natl. Acad. Sci. USA106, 2200.
Wang, Q., et al. 2008. J. Biol. Chem.283, 7445.
Fiebiger, E., et al. 2004. Mol. Biol. Cell15, 1635.

Informações legais

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Informações de segurança

• Código de classe de armazenamento: 11 - Combustible Solids
• Classe de risco de água (WGK): WGK 3
• Ponto de fulgor (°F): Not applicable
• Ponto de fulgor (°C): Not applicable