IACS-010759 (IACS-10759)

For research use only.

Catalog No.S8731

9 publications

IACS-010759 (IACS-10759) Chemical Structure

CAS No. 1570496-34-2

IACS-010759 (IACS-10759) is a potent and selective oxidative phosphorylation inhibitor (IC50 < 10 nM) that blocks cellular respiration through inhibition of complex I.

Selleck's IACS-010759 (IACS-10759) has been cited by 9 publications

Purity & Quality Control

Choose Selective OXPHOS Inhibitors

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].

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Z-138 NX\VUWR3WHKxbHnm[ZJifGmxbjDhd5NigQ>? MmjuO|IhcA>? MorRTWFEWy1yMUC3OVkhcW6qaXLpeIVlKHSqZTDwdo9tcW[ncnH0bY9vKG:oIGqtNVM5KGmwIHGg[I9{\WSncHXu[IVvfCCvYX7u[ZIh[XRibnHuc41wdGG{IHPvcoNmdnS{YYTpc45{ MnTEQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzFyNki0OFAoRjNzME[4OFQxRC:jPh?=
Maver-1 NVzEZXpEWHKxbHnm[ZJifGmxbjDhd5NigQ>? NF\5TGQ4OiCq MkniTWFEWy1yMUC3OVkhcW6qaXLpeIVlKHSqZTDwdo9tcW[ncnH0bY9vKG:oIF3heoVzNTFiaX6gZUBld3OnZHXw[Y5l\W62IH3hco5meiCjdDDuZY5wdW:uYYKgZ49v[2WwdILheIlwdnN? MkT0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzFyNki0OFAoRjNzME[4OFQxRC:jPh?=
H1975 NVzkW2RjWHKxbHnm[ZJifGmxbjDhd5NigQ>? NIKxPHczKGSjeYO= MmnvbIF{KGyrbXn0[YQh\W[oZXP0JI9vKGOnbHygdJJwdGmoZYLheIlwdg>? MWW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODZ{NUOyPUc,OzB4MkWzNlk9N2F-
CLL cells NGD0W5FHfW6ldHnvckBie3OjeR?= M4nvOVExOCCwTR?= NHW4RWczPCCq Mo\NbY5pcWKrdIOgU2NTKGGwZDDpcoNz\WG|ZYOg[4x6[2:ueYPpd{BqdiCFTFygZ4VtdHN? M3TqZ|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7OE[xPFQ4Lz5{OUi2NVg1PzxxYU6=

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
Cyto c / VDAC1 / β-Actin; 

PubMed: 32847115     


IACS-010759 and venetoclax cooperatively induce intrinsic apoptosis. (a) MV4-11 cells cultured in media supplemented with glucose were treated with vehicle control, IACS-010759, venetoclax, or in combination for 4 or 8 h. Cellular fractionation was performed. Mitochondrial and cytosolic fractions were subjected to western blot analysis. This experiment was performed 2 independent times in triplicate. One representative image is shown.

Cleaved PARP / Cleaved Caspase 3 / GAPDH; 

PubMed: 29861847     


(F) Immunoblot showing cleaved PARP and cleaved caspase 3 proteins in untreated or treated cells. C; Control untreated; D, drug IACS-010759-treated. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) protein was used as loading control.

Actin / LC3B I / LC3B II; 

PubMed: 32792483     


(h) Viable bone marrow AML blasts from mice treated with IACS-010759 (one experiment) were subjected to Western blot analysis for actin and LC3B. Numbers indicate ratios obtained by densitometric analysis.

32847115 29861847 32792483
Growth inhibition assay
Tumor Volume; 

PubMed: 32581056     


8 Gy×3 might be the most optimal radiotherapy (XRT) dose and fractionation scheme when combined with IACS-010759. Mice (six per group) were injected subcutaneously with 1×105 PD-1-resistant cells into the right leg and tumors were harvested on day 18. Three radiation schemes were chosen for comparison: 12 Gy×2 fractions, 8 Gy×3 fractions, and 6 Gy×3 fractions. IACS-010759 was administrated as per the protocol described in the text. Thus, the experiment had eight groups: control, IACS-010759 alone, 12 Gy×2 XRT, 8 Gy×3 XRT, 6 Gy×3 XRT, 12 Gy×2 XRT combined with IACS-010759, 8 Gy×3 XRT combined with IACS-010759, and 6 Gy×3 XRT combined with IACS-010759. (A) Data are presented according to XRT scheme. Only 8 Gy×3 combined with IACS-010759 showed significantly increased efficacy compared with XRT alone (two-way ANOVA, p=0.003).

32581056
IHC
pimonidazole stain; 

PubMed: 30787016     


(B) Representative pimonidazole staining analysis results of ICr A375-R1 xenografts treated for 1 week with IACS-010759 (5 mg/kg PO once daily) or vehicle.

pimonidazole stain of skull section; 

PubMed: 32695673     


Evaluation of the effect of Complex I inhibitor (OxPhosi) on BM hypoxia using pimonidazole IHC. (A,C) representative IHC of skull section of untreated leukemic mouse and (B,D) IHC of skull section of IACS-010759 treated mouse.

H&E stain; 

PubMed: 32695673     


Evaluation of the effect of Complex I inhibitor (OxPhosi) on BM hypoxia using pimonidazole IHC. (E,F) H&E on corresponding adjacent sections.

30787016 32695673
Immunofluorescence
Bodipy 493-503 / DAPI; 

PubMed: 32792483     


(e) Viable bone marrow AML blasts from mice treated with IACS-010759 were stained for Bodipy 493/503 and DAPI. Scale bar: 10 µm.

VDAC1 : IP3R1; 

PubMed: 32792483     


(i) Purified viable bone marrow AML blasts from mice treated with IACS-010759 (one experiment) were subjected to PLA assay.

32792483

Protocol

Cell Research:

[2]

- Collapse
  • 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.


    (Only for Reference)

Solubility (25°C)

In vitro DMSO 27 mg/mL (47.99 mM)
Water Insoluble
Ethanol 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.

Chemical Information

Molecular Weight 562.56
Formula

C25H25F3N6O4S

CAS No. 1570496-34-2
Storage powder
in solvent
Synonyms N/A
Smiles CC1=NC(=NN1CC2=CC(=CC=C2)N3CCC(CC3)S(=O)(=O)C)C4=NC(=NO4)C5=CC=C(C=C5)OC(F)(F)F

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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.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID