AK-7, SIRT2 Inhibitor

AK-7 is a cell- and brain-permeable, selective sirtuin SIRT2 inhibitor (IC50 ~15.5 μM). AK-7 displays no effect on SIRT1 or SIRT3. It diminishes neuronal cell death induced by mutant huntingtin fragment. It also down-regulates cholesterol biosynthetic gene expression and reduces total cholesterol levels in neurons in vivo. In two genetic mouse models of Huntington’s disease, AK-7 treatment resulted in improved motor function, extended survival, and reduced brain atrophy. AK-7 is a good chemical probe to study SIRT2’s roles in metabolic diseases, cancer, age-related disorders, and neurodegenerative diseases.

Product information

CAS Number: 420831-40-9

Molecular Weight: 437.35

Formula: C19H21BrN2O3S

Chemical Name: N-hydroxycyclopent-1-enecarboxamide

Smiles: O=C(NC1=CC(Br)=CC=C1)C1=CC(=CC=C1)S(=O)(=O)N1CCCCCC1

InChiKey: IYAYHZZWYNXHEQ-UHFFFAOYSA-N

InChi: InChI=1S/C19H21BrN2O3S/c20-16-8-6-9-17(14-16)21-19(23)15-7-5-10-18(13-15)26(24,25)22-11-3-1-2-4-12-22/h5-10,13-14H,1-4,11-12H2,(H,21,23)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO up to 100 mM

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

AK-7 was used at 10-25 µM in vitro and in cellular assays.

In Vivo:

AK-7 was administered by intraperitoneal injection to mice at 15-30 mg/kg/dose twice daily (formulation: 1.5 mg/mL in 25% Cremophor/10% DMSO in water).

References:

1. Taylor DM, et al. A brain-permeable small molecule reduces neuronal cholesterol by inhibiting activity of sirtuin 2 deacetylase. (2011) ACS Chem Biol. 6(6):540-6.
2. Chopra V, et al. The sirtuin 2 inhibitor AK-7 is neuroprotective in Huntington's disease mouse models. (2012) Cell Rep. 2(6):1492-7.

Products are for research use only. Not for human use.