AK-7

SKU: orb1301747

Description

AK-7 is a brain-permeable small molecule inhibitor of SIRT2 with an IC50 of 15.5 µM. It has been investigated in vitro for its potential to reduce neuronal cholesterol, supporting research in neurodegenerative disease models such as Parkinson's and Huntington's disease.

Research Area

Epigenetics & Chromatin, Molecular Biology

Key Properties

• CAS Number: 420831-40-9
• MW: 437.35
• Purity: 99.34% (May vary between batches)
• Formula: C₁₉H₂₁BrN₂O₃S
• SMILES: Brc1cccc(NC(=O)c2cccc(c2)S(=O)(=O)N2CCCCCC2)c1
• Target: Sirtuin
• Solubility: DMSO:50 mg/mL (114.32 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.57 mM)

Bioactivity

• Target IC50:
  SIRT2:15.5 μM
• In Vivo:
  AK-7 (15 mg/kg/dose, i.p.) is brain-permeable in both wild-type and HD mice.
• In Vitro:
  AK-7 is a selective cell- and brain-permeable SIRT2 inhibitor,this SIRT2 inhibitor stimulated cytoplasmic retention of sterol regulatory element binding protein-2 and subsequent transcriptional downregulation of cholesterol biosynthesis genes, resulting in reduced total cholesterol in primary striatal neurons. Furthermore, the identified inhibitor reduced cholesterol in cultured na ve neuronal cells and brain slices from wild-type mice.AK-7 has roles in metabolic diseases, cancer, age-related disorders, and neurodegenerative diseases, potentially including Alzheimer's, Huntington's, and Parkinson's diseases.
• Cell Research:
  Neuronal nuclear antigen (NeuN)-positive neurons and some astroglia were derived from mechanically dissociated ganglionic eminences of E16 rat embryos. The HD model based on the expression of mutant huntingtin has been described previously. Treatments of cultures with AK-7 were at 10 μM for 24 h unless stated otherwise. DMSO was included at the same concentrations as a control. Lower dose, chronic treatments with AK-7 were introduced to neurons at DIV4 and continued weekly coinciding with normal medium change .
• Animal Research:
  AK-7, solubilized at 1.5 mg/mL in 25% Cremophor EL (BASF)/ 10% DMSO in water, was administered by intraperitoneal injection to 11 week old mice at 15 mg/kg/dose. Blood was collected and centrifuged at 7,000 rpm for 7 min, and then serum was aspirated and immediately frozen in liquid nitrogen. Brains were immediately frozen in liquid nitrogen and stored at -80 C. Brains were weighed and then homogenized in four volumes of 10% Cremophor RH40 in water using homogenizer, and 2% v/v phosphoric acid was added to the homogenate, vortexed, and centrifuged at 10,000g at 25 C for 1 h. The supernatant was aspirated, and solid phase extraction was performed immediately. Serum samples were vortexed into 2% v/v phosphoric acid and centrifuged at 2500 rpm for 10 min

Storage & Handling

• Storage: keep away from moisture,store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

AK 7, AK7, AK-7, Inhibitor, inhibit, SIRT2, Sirtuin

Compound Identifiers

PubChem CID

1328033