IACS-010759 (IACS-10759)

Catalog No.S8731 Batch:S873106

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Technical Data

Formula

C25H25F3N6O4S
Molecular Weight 562.56 CAS No. 1570496-34-2
Solubility (25°C)* In vitro DMSO 33 mg/mL (58.66 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
0.5mg/ml Taking the 1 mL working solution as an example, add 50 μL of 10 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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 IACS-010759 (IACS-10759) is a potent and selective oxidative phosphorylation inhibitor (IC50 < 10 nM) that blocks cellular respiration through inhibition of complex I.
Targets
oxidative phosphorylation [2]
10 nM
In vitro

IACS-010759 significantly reduced viability measured by CTG assay in all cell lines tested (Notch mutant: Pf382, 1301, Jurkat, MOLT-4, P12-Ichikawa and Notch wt: T-ALL1). Treatment of T-ALL with IACS-010759 had effectively inhibited FA-stimulated mitochondrial respiration indicated by decreased oxygen consumption rates (OCR). However, the cells maintain an ability to generate energy via glycolysis, indicated by high extracellular acidification rate (ECAR) in both, control and IACS-treated groups[1].

In CLL cells, IACS-010759 causes minimal cell death, inhibits oxygen consumption rate (OCR) and increases glycolysis. It also decreases intracellular ribonucleotide triphosphate pools in CLL[2].

In sensitive AML cells IACS-010759 induces AMPK activation leading to mTOR suppression which results in cell growth inhibition in AML cells. AMPK and mTOR could be putative biomarkers of anti-leukemia activity of the novel OxPhosi IACS-010759[3].
In vivo

IACS-010759 is a potent inhibitor of mitochondria complex I of the electron transport chain. It inhibits proliferation and induces apoptosis in models of brain cancer and acute myeloid leukemia (AML) reliant on oxidative phosphorylation.[4]

Protocol (from reference)

Cell Assay:

[2]
  • Cell lines

    CLL cells

  • Concentrations

    30 nM, 100 nM, 300 nM, 1 μM, and 3 μM

  • Incubation Time

    24 or 48 h

  • Method

    CLL cells are treated with IACS-010759 for 24 or 48 h and were then stained with acridine orange and analyzed by flow cytometry.

Selleck's IACS-010759 (IACS-10759) has been cited by 39 publications

Mitochondrial complex I promotes kidney cancer metastasis [ Nature, 2024, 10.1038/s41586-024-07812-3] PubMed: 39143213
Compensatory activity of the PC-ME1 metabolic axis underlies differential sensitivity to mitochondrial complex I inhibition [ Nat Commun, 2024, 15(1):8682] PubMed: 39375345
Self-renewing human naïve pluripotent stem cells dedifferentiate in 3D culture and form blastoids spontaneously [ Nat Commun, 2024, 15(1):668] PubMed: 38253551
Cyclin-dependent kinase 12 deficiency reprogrammes cellular metabolism to alleviate ferroptosis potential and promote the progression of castration-resistant prostate cancer [ Clin Transl Med, 2024, 14(5):e1678] PubMed: 38736108
Deoxycytidine kinase inactivation enhances gemcitabine resistance and sensitizes mitochondrial metabolism interference in pancreatic cancer [ Cell Death Dis, 2024, 15(2):131] PubMed: 38346958
Multivariate analysis of metabolic state vulnerabilities across diverse cancer contexts reveals synthetically lethal associations [ Cell Rep, 2024, 43(10):114775] PubMed: 39305483
Preneoplastic cells switch to Warburg metabolism from their inception exposing multiple vulnerabilities for targeted elimination [ Oncogenesis, 2024, 13(1):7] PubMed: 38272902
Characterizing OXPHOS inhibitor-mediated alleviation of hypoxia using high-throughput live cell-imaging [ Cancer Metab, 2024, 12(1):13] PubMed: 38702787
Targeting metabolic adaptive responses induced by glucose starvation inhibits cell proliferation and enhances cell death in osimertinib-resistant non-small cell lung cancer (NSCLC) cell lines [ Biochem Pharmacol, 2024, S0006-2952(24)00144-8] PubMed: 38522556
Targeting Asparagine Metabolism in Well-Differentiated/Dedifferentiated Liposarcoma [ Cancers (Basel), 2024, 16(17)3031] PubMed: 39272889

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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.

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