ND646

For research use only.

Catalog No.S8377

ND646 Chemical Structure

CAS No. 1434639-57-2

ND-646 is an allosteric inhibitor of the ACC (Acetyl-coA carboxylase) enzymes that prevents ACC subunit dimerization to suppress fatty acid synthesis with IC50 of 3.5 nM and 4.1 nM for hACC1 and hACC2, respectively.

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Choose Selective Acetyl-CoA carboxylase Inhibitors

Biological Activity

Description ND-646 is an allosteric inhibitor of the ACC (Acetyl-coA carboxylase) enzymes that prevents ACC subunit dimerization to suppress fatty acid synthesis with IC50 of 3.5 nM and 4.1 nM for hACC1 and hACC2, respectively.
Targets
hACC1 [1]
(Cell-free assay)
hACC2 [1]
(Cell-free assay)
3.5 nM 4.1 nM
In vitro

ND-646 inhibits FASyn in vitro and induces apoptosis in NSCLC cells. AMPK phosphorylation sites can be used as a biomarker to monitor ACC engagement by ND-646.[1]

In vivo

Chronic ND-646 treatment of xenograft and genetically engineered mouse models of NSCLC inhibits tumor growth. When administered as a single agent or in combination with the standard-of-care drug carboplatin, ND-646 markedly suppresses lung tumor growth in the Kras;Trp53−/− (also known as KRAS p53) and Kras;Stk11−/− (also known as KRAS Lkb1) mouse models of NSCLC.[1]

Protocol

Cell Research:

[1]

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  • Cell lines: A549 cells
  • Concentrations: 7 nM, 21 nM, 62 nM, 185 nM, 555 nM, 1666 nM, 5000 nM
  • Incubation Time: 24 hrs
  • Method:

    All cell lines are incubated at 37 ℃ and are maintained in an atmosphere containing 5% CO2. A549, H460, H157 and H1355 cells are purchased from the ATCC. Cells are tested for Mycoplasma using manufacturer's conditions and are deemed negative. Cells are grown in Dulbecco's modified Eagles medium (DMEM) plus 10% fetal bovine serum. ACC1-KO clones are maintained in 10% FBS + addition of 200 μM palmitate every 3 days. For proliferation assays via cell counts, cells are plated into 24 well plates in triplicate at 2E4 cells/well and the following day treated with either DMSO vehicle or ND-646. Cell counts are recorded at days 1, 3, 5 and 7-post treatment. For delipidated media, cells are first seeded in media containing regular 10% FBS and the following day are switched into media containing 20% delipidated FBS upon treatment. Viability assays are performed using either a WST-1 viability assay or Cyquant in 96 well culture plates under manufacturers conditions. For quantitation, values from treated cells are divided by values from control treated cells and expressed as percent control. Palmitate rescue experiments are performed in delipidated media by co-treating cells, in 24 well plates, with ND-646 and 200 μM of palmitate conjugated to BSA. For palmitate-BSA preparation, palmitate is solubilized in 100% Etoh @ 50 mM and combined with 4% fatty acid free BSA in saline at a ratio of 1:4 to make a palmitate concentration of 10 mM. Palmitate-BSA is used at a final concentration of 200 μM.


    (Only for Reference)
Animal Research:

[1]

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  • Animal Models: female athymic nude mice
  • Dosages: 25 mg/kg, 50 mg/kg
  • Administration: Oral gavage
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 100 mg/mL (175.85 mM)
Water Insoluble
Ethanol '''100 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 568.64
Formula

C28H32N4O7S

 

CAS No. 1434639-57-2
Storage powder
in solvent
Synonyms N/A

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID