EX 527

Product Description

EX 527 is a selective inhibitor of SIRT1 that does not inhibit histone deacetylase (HDAC) or other sirtuin deacetylase family members (IC₅₀ values are 98, 19600, 48700, > 100000 and > 100000 nM for SIRT1, SIRT2, SIRT3, HDAC and NADase respectively). In an animal model of Huntington's disease, EX 527 rescues neuronal degeneration, extends lifespan, reduces huntingtin inclusions and prevents ventricular enlargement. EX 527 enhances p53 acetylation in response to DNA damaging agents. Orally bioavailable and brain penetrant.

Solubility

Preparing Stock Solutions for EX 527

The following data is based on the product molecular weight 248.71

Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which all affect the solvent volumes required to prepare stock solutions.

Select a batch to recalculate based on the batch molecular weight:

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Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
0.75 mM	5.36 mL	26.80 mL	53.61 mL
3.75 mM	1.07 mL	5.36 mL	10.72 mL
7.5 mM	0.54 mL	2.68 mL	5.36 mL
37.5 mM	0.11 mL	0.54 mL	1.07 mL

Calculators

Background References

References are publications that support the biological activity of the product.

• Smith A potent and selective Sirtuin 1 inhibitor alleviates pathology in multiple animal and cell models of Huntington's disease. Hum. Mol. Genet. 2014 PMID: 24436303
• Napper Discovery of indoles as potent and selective inhibitors of the deacetylase SIRT1. J.Med.Chem. 2005 PMID: 16335928
• Zhao The 2.5 Å crystal structure of the SIRT1 catalytic domain bound to nicotinamide adenine dinucleotide (NAD⁺) and an indole (EX527 analogue) reveals a novel mechanism of histone deacetylase inhibition. J.Med.Chem. 2013 PMID: 23311358
• Solomon Inhibition of SIRT1 catalytic activity increases p53 acetylation but does not alter cell survival following DNA damage. Mol.Cell.Biol. 2006 PMID: 16354677