GLPBio

Nonactin

Catalog No.: GC12090Purity:>95.00%
COASDSData Sheet
Nonactin is a macrotetrolide antibiotic and mitochondrial oxidative phosphorylation uncoupler.

Products are for research use only. Not for human use. We do not sell to patients.

Nonactin
Cas No.: 6833-84-7
5mgIn Stock
$75.00
1
10mgIn Stock
$134.00
1
25mgIn Stock
$295.00
1
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Description

Nonactin is a macrotetrolide antibiotic and mitochondrial oxidative phosphorylation uncoupler[1][2]. Nonactin inhibits recombinant human adenine nucleotide translocase (ANT) isoforms ANT1–4 with IC50 values of 4.4, 3.3, 4.7, and 3.3μM, respectively[3]. Nonactin is commonly used in studies of oxidative-phosphorylation uncoupling, ionophore mechanisms, and apoptosis in β-catenin-mutant tumors[4].

In vitro, treatment of BHK cells with Nonactin (5μg/ml; 12-14h) blocks cell-surface expression of NDV-HN and VSV-G glycoproteins without reducing their total synthesis, causes intracellular accumulation of VSV-G, inhibits syncytium formation and lowers infectious-virus yield[5]. Treatment of medullary thyroid carcinoma TT cells with Nonactin (0.12-0.5µM; 72h) reduces RET protein and mRNA level, suppresses pAKT/pmTOR signaling, induces G1 arrest, lowers cyclin D1/E, E2F1 and BCL-2, increases γH2AX and cleaved PARP, and elevates caspase-3/7 activity[6].

In vivo, Nonactin (100mg/kg/day; i.p.; 4 days) induced marked tumor regression and robust TUNEL-positive apoptosis in β-catenin-mutant HCT 116 xenograft mice without significant body-weight loss[7].

References:
[1] Pampaloni F, Mayer B, Kabat Vel-Job K, et al. A Novel Cellular Spheroid-Based Autophagy Screen Applying Live Fluorescence Microscopy Identifies Nonactin as a Strong Inducer of Autophagosomal Turnover. SLAS Discov. 2017;22(5):558-570.
[2] Martínez-Haya B, Avilés-Moreno JR, Hamad S, Elguero J. On the ionophoric selectivity of nonactin and related macrotetrolide derivatives. Phys Chem Chem Phys. 2017;19(2):1288-1297.
[3] Zhang Y, Tian D, Matsuyama H, et al. Human Adenine Nucleotide Translocase (ANT) Modulators Identified by High-Throughput Screening of Transgenic Yeast. J Biomol Screen. 2016;21(4):381-390.
[4] Hu J, Zhang J, He J. Structures, Synthesis and Biological Activities of Nonactic Acid and Its Derivatives. Curr Med Chem. 2021;28(42):8673-8691.
[5] Lee JM, Kim JG, Kim TH, et al. Nonactin hinders intracellular glycosylation in virus-infected baby hamster kidney cells. Mol Med Rep. 2010;3(1):115-119.
[6] Alqahtani T, Alsubait A, Aloumi M, et al. A novel role for nonactin: interfering with G-quadruplex in RET-driven medullary thyroid cancer. BMC Cancer. 2024;24(1):1569.
[7] Shikata Y, Kiga M, Futamura Y, et al. Mitochondrial uncoupler exerts a synthetic lethal effect against β-catenin mutant tumor cells. Cancer Sci. 2017;108(4):772-784.

Protocol

Cell experiment [1]:

Cell lines

MTC-derived TT cells

Preparation Method

The MTC-derived TT cells were cultured in DMEM/F12 medium enriched with 15% heat-inactivated fetal bovine serum (FBS) and maintained under a humidified atmosphere with 5% CO2 at 37°C. Cells were plated at 7,500 cells per well in a 96-well plate and allowed to adhere overnight. Following this, they were exposed to various concentrations of Nonactin (0.12-0.5µM) for up to 72h. To evaluate cell viability, a solution of 0.33mg/mL MTS dye mixed with 200µg/mL phenazine methosulfate (PMS) was used. Absorbance readings were taken at 490nm. Caspase-3 activity in TT cells was evaluated utilizing the ApoAlert Caspase Fluorescent Assay kit. And cells were collected for PCR and Western blot analyses.

Reaction Conditions

0.12-0.5µM; 72h

Applications

Treatment of medullary thyroid carcinoma TT cells with Nonactin reduces RET protein and mRNA level, suppresses pAKT/pmTOR signaling, lowers cyclin D1/E, E2F1 and BCL-2, increases γH2AX and cleaved PARP, and elevates caspase-3/7 activity.

Animal experiment [2]:

Animal models

BALB/cA Jcl-nu mice

Preparation Method

Specific pathogen-free female nude mice (BALB/cA Jcl-nu) were used in this experiment. β-catenin-mutant HCT 116 cells (2×106cells/mL) were inoculated subcutaneously into the axillar region of the nude mice on Day 0. Nonactin was dissolved in 10% dimethylacetamide, 10% NIKKOL HCO60, and saline and given daily to the animals by intraperitoneal administration (100mg/kg). Tumor-bearing nude mice were randomly grouped (six mice/group), and administration of nonactin started on Day 9 to Day 12. Tumor volumes were calculated using a microgauge according to the following equations: Tumor volume (mm3)=1/2×(tumor length)×(tumor width)2. TUNEL staining of xenograft tumor tissue was performed using the FragEL DNA Fragmentation Detection Kit according to the manufacturer’s protocol. Tissue sections were viewed at 100×magnification, and images were captured with a digital camera.

Dosage form

100mg/kg/day; i.p.; 4 days

Applications

Nonactin (100mg/kg/day; i.p.; 4 days) induced marked tumor regression and robust TUNEL-positive apoptosis in β-catenin-mutant HCT 116 xenograft mice without significant body-weight loss[7].

References:
[1] Alqahtani T, Alsubait A, Aloumi M, et al. A novel role for nonactin: interfering with G-quadruplex in RET-driven medullary thyroid cancer. BMC Cancer. 2024;24(1):1569.
[2] Shikata Y, Kiga M, Futamura Y, et al. Mitochondrial uncoupler exerts a synthetic lethal effect against β-catenin mutant tumor cells. Cancer Sci. 2017;108(4):772-784.

Product Documents

Purity:>95.00%Appearance:A solid
COASDSData Sheet

Chemical Properties

CAS No.
6833-84-7
Chemical Name
(1R,2R,5R,7R,10S,11S,14S,16S,19R,20R,23R,25R,28S,29S,32S,34S)-2,5,11,14,20,23,29,32-octamethyl-4,13,22,31,37,38,39,40-octaoxapentacyclo[32.2.1.17,10.116,19.125,28]tetracontane-3,12,21,30-tetrone
SMILES
O=C([C@H](C)[C@@H]1O[C@H]2CC1)O[C@H](C)C[C@@H]3O[C@H]([C@H](C)C(O[C@@H](C)C[C@H]4O[C@@H]([C@@H](C)C(O[C@H](C)C[C@@H]5O[C@H]([C@H](C)C(O[C@@H](C)C2)=O)CC5)=O)CC4)=O)CC3
Molecular Formula
C40H64O12
Molecular Weight
736.94
Solubility
1mg/mL in ethanol, 0.25mg/mL in DMSO, 10mg/mL in DMF
Storage
Desiccate at -20°C
General tips
Select a suitable solvent according to the product solubility data. Once prepared, aliquot the stock solution to avoid repeated freeze-thaw cycles.
Use stock solutions within 6 months when stored at -80°C or within 1 month when stored at -20°C.
To improve solubility, warm the tube to 37°C and sonicate it for an appropriate period.
Shipping Condition
Evaluation samples are shipped with blue ice. Other available sizes are shipped at room temperature or with blue ice upon request.

CalculatorsMolarity / Dilution / Molecular Weight / Unit Conversion / In Vivo Formulation / Solubility

g/mol

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