ND646

Catalog No.S8377 Batch:S837701

Technical Data

Formula	C₂₈H₃₂N₄O₇S
Molecular Weight	568.64	CAS No.	1434639-57-2
Solubility (25°C)*	In vitro	DMSO	100 mg/mL (175.85 mM)
		Ethanol	100 mg/mL (175.85 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * 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. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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, 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 (from reference)

Cell Assay:^{^[1]}	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 2^E4 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.
Animal Study:^{^[1]}	Animal Models female athymic nude mice Dosages 25 mg/kg, 50 mg/kg Administration Oral gavage

Cell Assay:^{^[1]}

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 2^E4 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.

Animal Study:^{^[1]}

Animal Models
female athymic nude mice
Dosages
25 mg/kg, 50 mg/kg
Administration
Oral gavage

References

[1] Robert U Svensson, et al. Nat Med. 2016 Oct;22(10):1108-1119.

Selleck's ND646 has been cited by 3 publications

Dysregulated Lipid Synthesis by Oncogenic IDH1 Mutation Is a Targetable Synthetic Lethal Vulnerability [ Cancer Discov, 2023, 13(2):496-515]	PubMed: 36355448
A subset of VEGFR-TKIs activates AMPK in LKB1-mutant lung cancer [ Cancer Sci, 2023, 114(4):1651-1662]	PubMed: 36459496
A subset of VEGFR-TKIs activates AMPK in LKB1-mutant lung cancer [ Cancer Sci, 2023, 114(4):1651-1662]	PubMed: 36459496

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.