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AK-1

Names

[ CAS No. ]:
330461-64-8

[ Name ]:
AK-1

[Synonym ]:
3-(1-Azepanylsulfonyl)-N-(3-nitrophenyl)benzamide
Benzamide, 3-[(hexahydro-1H-azepin-1-yl)sulfonyl]-N-(3-nitrophenyl)-
sirt2 inhibitor ii, ak-1
AK-1

Biological Activity

[Description]:

AK-1 is a potent, specific and cell-permeable SIRT2 inhibitor.

[Related Catalog]:

Research Areas >> Neurological Disease

[Target]

SIRT2


[In Vitro]

AK-1 achieves significant neuroprotection in Huntington’s disease flies at 10 μM, improving the number of rhabdomeres from 5.2 to 5.6[1]. AK-1 treatment induces proteasomal degradation of the Snail transcription factor through inactivation of the NF-κB/CSN2 pathway. Reduction in the level of Snail results in upregulation of p21, leading to G1 arrest, slow proliferation, and slow wound-healing activity. The regulation of Snail-p21 axis by AK-1 also occurs in HT-29 colon cancer cells[2]. Under hypoxic conditions, AK-1 increases the ubiquitination of HIF-1α in a VHL-dependent manner, leading to the degradation of HIF-1α via a proteasomal pathway. Downregulation of HIF-1α expression reduces its transcriptional activity and, eventually, reduces the expression of BNIP3, one of HIF-1 target genes, in AK-1-treated cells[3].

[Cell Assay]

HEK293 cells are co-transfected with 3 μg of pGL2-PGK1-HRE-Luc and 1 μg of pCMV-β-galactosidase plasmids. Twenty-four hours later, the cells are incubated under hypoxic conditions for 24 hr in the presence of 10 μM AK-1 and then lysed with luciferase cell lysis buffer. Luciferase and β-galactosidase activities are measured using luciferin and ο-nitrophenyl-β-d-galactopyranoside, respectively, as substrates. Transfection efficiency is normalized according to β-galactosidase activity[3].

[References]

[1]. Luthi-Carter R, et al. SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis. Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7927-32.

[2]. Cheon MG, et al. AK-1, a specific SIRT2 inhibitor, induces cell cycle arrest by downregulating Snail in HCT116 human colon carcinoma cells. Cancer Lett. 2015 Jan 28;356(2 Pt B):637-45.

[3]. Lee SD, et al. AK-1, a SIRT2 inhibitor, destabilizes HIF-1α and diminishes its transcriptional activity during hypoxia. Cancer Lett. 2016 Apr 1;373(1):138-45.


[Related Small Molecules]

Selisistat (EX 527) | Nicotinamide | SRT1720 HCl | Sirtinol | 3-TYP | SRT 2104 | Fisetin | OSS_128167 | Thiomyristoyl | Cambinol | Tenovin-1 | CAY10602 | AK-7 | Inauhzin | Tenovin 6 Hydrochloride

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Molecular Formula ]:
C19H21N3O5S

[ Molecular Weight ]:
403.452

[ Exact Mass ]:
403.120178

[ PSA ]:
120.68000

[ LogP ]:
4.11

[ Index of Refraction ]:
1.630

[ Storage condition ]:
2-8℃

Safety Information

[ RIDADR ]:
NONH for all modes of transport


Related Compounds