AK-1

Cat No.:V6633 Purity: ≥98%

COA Product Data Instructions for use SDS

AK-1 is a potent, specific and cell-penetrating/penetrable SIRT2 inhibitor (antagonist) with IC50 of 12.5 μM.

AK-1 Chemical Structure CAS No.: 330461-64-8
Product category: Sirtuin

This product is for research use only, not for human use. We do not sell to patients.

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Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

AK-1 is a potent, specific and cell-penetrating/penetrable SIRT2 inhibitor (antagonist) with IC50 of 12.5 μM.

Biological Activity I Assay Protocols (From Reference)

ln Vitro	On Drosophila with Huntington's disease, AK-1 at 10 μM had a strong neuroprotective effect, increasing the number of striated muscles from 5.2 to 5.6 [1]. With an IC50 of 12.5 μM, AK-1 is a powerful, selective, and cell-permeable inhibitor of SIRT2 [2]. By blocking the NF-κB/CSN2 pathway, AK-1 therapy causes the Snail transcription factor to be broken down by proteases. Decreased snail levels cause p21 to be overexpressed, which slows down wound healing, G1 arrest, and proliferation. In HT-29 colon cancer cells, AK-1 also regulates the Snail-p21 axis [3]. In hypoxic environments, AK-1 enhances HIF-1α's ubiquitination in a VHL-dependent manner, which triggers HIF-1α's destruction via the proteasomal route. Downregulating HIF-1α expression in AK-1-treated cells lowers its transcriptional activity, which in turn lowers the expression of BNIP3, one of the HIF-1 target genes [4].
References	[1]. SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis. Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7927-32. [2]. AK-1, a SIRT2 inhibitor, destabilizes HIF-1α and diminishes its transcriptional activity during hypoxia. Cancer Lett. 2016 Apr 1;373(1):138-45. [3]. SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis. Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7927-32. [4]. A Brain-Permeable Small Molecule Reduces Neuronal Cholesterol by Inhibiting Activity of Sirtuin 2 Deacetylase. ACS Chem Biol. 2011 Jun 17;6(6):540-6. [5]. 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.

ln Vitro

On Drosophila with Huntington's disease, AK-1 at 10 μM had a strong neuroprotective effect, increasing the number of striated muscles from 5.2 to 5.6 [1]. With an IC50 of 12.5 μM, AK-1 is a powerful, selective, and cell-permeable inhibitor of SIRT2 [2]. By blocking the NF-κB/CSN2 pathway, AK-1 therapy causes the Snail transcription factor to be broken down by proteases. Decreased snail levels cause p21 to be overexpressed, which slows down wound healing, G1 arrest, and proliferation. In HT-29 colon cancer cells, AK-1 also regulates the Snail-p21 axis [3]. In hypoxic environments, AK-1 enhances HIF-1α's ubiquitination in a VHL-dependent manner, which triggers HIF-1α's destruction via the proteasomal route. Downregulating HIF-1α expression in AK-1-treated cells lowers its transcriptional activity, which in turn lowers the expression of BNIP3, one of the HIF-1 target genes [4].

References

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

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

[3]. SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis. Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7927-32.

[4]. A Brain-Permeable Small Molecule Reduces Neuronal Cholesterol by Inhibiting Activity of Sirtuin 2 Deacetylase. ACS Chem Biol. 2011 Jun 17;6(6):540-6.

[5]. 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.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Exact Mass	403.12
CAS #	330461-64-8
PubChem CID	1341463
Appearance	White to off-white solid powder
Density	1.4±0.1 g/cm3
Index of Refraction	1.630
LogP	4.11
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	4
Heavy Atom Count	28
Complexity	650
Defined Atom Stereocenter Count	0
SMILES	S(C1=C([H])C([H])=C([H])C(C(N([H])C2C([H])=C([H])C([H])=C(C=2[H])[N+](=O)[O-])=O)=C1[H])(N1C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H])(=O)=O
InChi Key	HAYBKCHPEBZNGW-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H21N3O5S/c23-19(20-16-8-6-9-17(14-16)22(24)25)15-7-5-10-18(13-15)28(26,27)21-11-3-1-2-4-12-21/h5-10,13-14H,1-4,11-12H2,(H,20,23)
Chemical Name	3-(azepan-1-ylsulfonyl)-N-(3-nitrophenyl)benzamide
HS Tariff Code	2934.99.9001
Storage	Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)	DMSO : ≥ 50 mg/mL (~123.93 mM)
Solubility (In Vivo)	Solubility in Formulation 1: ≥ 2.5 mg/mL (6.20 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.)

Solubility (In Vitro)

DMSO : ≥ 50 mg/mL (~123.93 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.20 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

(Please use freshly prepared in vivo formulations for optimal results.)

Calculator

Mass

Concentration

Volume

Molecular Weight*

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

Average weight of animals g

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Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

% ddH₂O

Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03210740	COMPLETED	Drug: AM001 Cream, 7.5% Drug: Vehicle Cream	Actinic Keratosis	AmDerma	2017-06-06	Phase 2
NCT06092346	RECRUITING		AK1, OMIM 103000, Adenylate Kinase Deficiency ADA2, OMIM 607575,Sneddon Syndrome; VAIHS ADSL, OMIM 608222, Adenylosuccinate Lyase Deficiency AICDA, OMIM 605257, Immunodeficiency With Hyper-IgM, Type 2; HIGM2		2023-12-19
NCT05865730	RECRUITING	Other: Live Bacterial Product - Akkermansia muciniphila	Carcinoma, Non-Small-Cell Lung Carcinoma, Renal Cell	EverImmune	2022-10-01	Phase 2

Biological Data

Neuroprotective effects of SIRT2 inhibitors in invertebrate models of HD. (A) AGK2 and AK-1 decrease the degeneration of light-sensing rhabdomeres in the Drosophila eye. *, P < 0.02 (for 10 μM AGK2 or AK-1, respectively). (B and C) Heterozygous and homozygous deletion of Sirt2 shows a dose-dependent reduction in the Drosophila model of HD. AK-1 (D) and AGK2 (E) rescued the defective touch response in C. elegans expressing polyQ N-ter Htt fused to CFP in touch receptor neurons. (*, P < 0.05).[1].Ruth Luthi-Carter, et al. SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis. Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7927-32.

SIRT2 inhibition protects against Htt171-82Q toxicity in primary striatal neurons. (A) As shown previously, Htt171-82Q (black bar) exhibits toxicity toward striatal neurons as compared with Htt171-18Q (white bar). AK-1 rescued Htt171-82Q-expressing cells in a dose-dependent manner (at concentrations of 1, 2, and 4 μM) (A) and significantly reduced the number of mutant Htt positive inclusions (B). AGK2 also rescued striatal neurons from Htt171-82Q toxicity (C) and significantly reduced the number of inclusions (D). Overexpression of SIRT2WT abrogates neuroprotection by AK-1 (E). A lentiviral vector encoding CFP is used as a coinfection control. A dominant negative deacetylase mutant SIRT2H150Y significantly decreases Htt171-82Q toxicity in primary striatal neurons (F) and also significantly reduced the number of inclusions (G). A lentiviral vector encoding CFP is used as a coinfection control (* P < 0.05).[1].Ruth Luthi-Carter, et al. SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis. Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7927-32.

Gene expression and metabolic effects of SIRT2 inhibition in neurons. (A) Multiple genes controlling sterol biosynthesis are down-regulated by AK-1 treatment. Scheme depicts enzymes in sterol biosynthesis whose RNAs are down-regulated by AK-1 treatment by the criterion of FDR P < 0.05. (The segment of the pathway between acetoacetate and cholesterol is shown.) Full analyses of the data, including statistical measures, fold-changes, and Gene Ontology analyses, are presented in Dataset S1 and S2. (B–D) SIRT2 inhibition reverses Htt171-82Q-mediated increase in sterols. (B) DMSO-treated neurons expressing Htt171-82Q had significantly higher sterol levels (cholesterol and cholesteryl esters) than those expressing either CFP or Htt171-18Q and this effect was reversed by treatment with AK-1, AGK2 (5 μM, 48 hrs) (C), and SIRT2H150Y (D) (*P < 0.05).[1].Ruth Luthi-Carter, et al. SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis. Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7927-32.