LY2109761

Catalog No.S2704 Batch:S270405

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Technical Data

Formula

C26H27N5O2
Molecular Weight 441.52 CAS No. 700874-71-1
Solubility (25°C)* In vitro DMSO 10.8 mg/mL (24.46 mM)
Water Insoluble
Ethanol 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.)

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Biological Activity

Description LY2109761 is a novel selective TGF-β receptor type I/II (TβRI/II) dual inhibitor with Ki of 38 nM and 300 nM in a cell-free assay, respectively; shown to negatively affect the phosphorylation of Smad2. LY2109761 blocks autophagy and induces apoptosis.
Targets
TβRI [1]
(Cell-free assay)		 TβRII [1]
(Cell-free assay)
38 nM(Ki) 300 nM(Ki)
In vitro LY2109761 treatment induces a dose-dependent low-anchorage growth inhibition of L3.6pl/GLT cells, leading to ~33% or 73% inhibition at 2 μM and 20 μM, respectively, which can be strongly enhanced when combined with gemcitabine in combination index value of 0.36581. Blocking TβRI/II kinase activity with LY2109761 (5 μM) completely suppresses both the basal and TGF-β1-stimulated migration and invasion of L3.6pl/GLT cells, significantly enhances the detachment-induced apoptosis by 26% at 8 hours treatment, and completely suppresses TGF-β–induced Smad2 phosphorylation. [1] LY2109761 treatment at 1 nM is sufficient to significantly block the migration and invasion but not adhesion of hepatocellular carcinoma cells by increasing E-cadherin expression. [2] LY2109761 pretreatment enhances radiosensitivity of glioblastoma cells via TGF-β signaling blockage. LY2109761 (10 μM) reduces the self-renewal and proliferation of GBM-derived cancer stem–like cells (CSLC), which can be significantly enhanced when combined with radiation. [3]
In vivo Administration of LY2109761 (50 mg/kg) alone or in combination with gemcitabine (25 mg/kg) significantly reduces the tumor volume by ~70% and ~90%, respectively, prolongs the survival with the median survival duration of 45.0 days and 77.5 days, respectively, and reduces spontaneous abdominal metastases in the L3.6pl/GLT Xenograft mice model. [1] In consistent with the in vitro effect, administration of LY2109761 alone or in combination with radiation, markedly inhibits tumor growth in the orthotopical CSLC glioblastoma model by 43.4% and 76.3%, respectively, decreases tumor invasion and tumor microvessel density, and significantly enhances radiation-induced tumor growth delay in the U87MG xenograft mice model. [3]

Protocol (from reference)

Cell Assay:[1]
  • Cell lines

    Colo357FG/GLT, and Colo357L3.6pl/GLT

  • Concentrations

    Dissolved in DMSO, final concentrations ~10 μM

  • Incubation Time

    48 hours

  • Method

    Cells are exposed to increasing doses of LY2109761 (~10 μM) for 48 hours. The medium containing drugs is removed, the cells are washed twice with PBS, and fresh medium is added. After 5 days of incubation, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay is used to obtain relative variable cell numbers.
Animal Study:[1]
  • Animal Models

    Athymic nude mice with orthotopic implantation of L3.6pl/GLT cells

  • Dosages

    50 mg/kg

  • Administration

    Twice a day p.o.

Customer Product Validation

Data from [Data independently produced by Invest Ophthalmol Vis Sci, 2014, 55(3), 1770-9]

Data from [Data independently produced by Toxicology, 2014, 326C, 9-17]

Data from [PLoS One, 2013, 8(12), e83521]

Data from [Data independently produced by , , Mol Cell Proteomics, 2016, 15(3):1017-31]

Selleck's LY2109761 has been cited by 131 publications

PALB2-mutated human mammary cells display a broad spectrum of morphological and functional abnormalities induced by increased TGFβ signaling [ Cell Mol Life Sci, 2024, 81(1):173] PubMed: 38597967
PALB2-mutated human mammary cells display a broad spectrum of morphological and functional abnormalities induced by increased TGFβ signaling [ Cell Mol Life Sci, 2024, 81(1):173] PubMed: 38597967
Serum-Induced Proliferation of Human Cardiac Stem Cells Is Modulated via TGFβRI/II and SMAD2/3 [ Int J Mol Sci, 2024, 25(2)959] PubMed: 38256034
Oxyberberine sensitizes liver cancer cells to sorafenib via inhibiting NOTCH1-USP7-c-Myc pathway [ Hepatol Commun, 2024, 8(4)e0405] PubMed: 38573832
TGF-β signaling promotes cervical cancer metastasis via CDR1as [ Mol Cancer, 2023, 22(1):66] PubMed: 37004067
Investigating the Role of TGF-β Signaling Pathways in Human Corneal Endothelial Cell Primary Culture [ Cells, 2023, 12(12)1624] PubMed: 37371094
FUT1-mediated terminal fucosylation acts as a new target to attenuate renal fibrosis [ Mol Med, 2023, 29(1):55] PubMed: 37085770
Gallium-modified gelatin nanoparticles loaded with quercetin promote skin wound healing via the regulation of bacterial proliferation and macrophage polarization [ Front Bioeng Biotechnol, 2023, 11:1124944] PubMed: 36777248
Identification of therapeutic sensitivities in a spheroid drug combination screen of Neurofibromatosis Type I associated High Grade Gliomas [ PLoS One, 2023, 18(2):e0277305] PubMed: 36730269
Heat treatment-induced autophagy promotes breast cancer cell invasion and metastasis via TGF-β2-mediated epithelial-mesenchymal transitions [ PeerJ, 2023, 11:e14640] PubMed: 36650834

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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.