LY2109761

製品コードS2704 バッチS270406

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C26H27N5O2
分子量 441.52 CAS No. 700874-71-1
Solubility (25°C)* 体外 DMSO 9 mg/mL (20.38 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 LY2109761は、新規の選択的TGF-β receptor type I/II (TβRI/II)デュアル阻害剤で、in vitroアッセイにおけるKi値はそれぞれ38 nMと300 nMです。Smad2のリン酸化に負の影響を与えることが示されています。LY2109761はautophagyを阻害し、apoptosisを誘発します。
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 in combination index value of 0.36581. Blocking TβRI/II kinase activity with this compound 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. This chemical 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. It pretreatment enhances radiosensitivity of glioblastoma cells via TGF-β signaling blockage. This compound reduces the self-renewal and proliferation of GBM-derived cancer stem–like cells (CSLC), which can be significantly enhanced when combined with radiation.

in vivo

Administration of LY2109761 (50 mg/kg) alone or in combination 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. In consistent with the in vitro effect, administration of this compound 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.

プロトコル(参考用のみ)

細胞アッセイ 細胞株 Colo357FG/GLT, and Colo357L3.6pl/GLT
濃度 Dissolved in DMSO, final concentrations ~10 μM
反応時間 48 hours
実験の流れ

Cells are exposed to increasing doses of LY2109761 (~10 μM) for 48 hours. The medium containing this compound 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.
動物実験 動物モデル Athymic nude mice with orthotopic implantation of L3.6pl/GLT cells
投薬量 50 mg/kg
投与方法 Twice a day p.o.

参考

  • https://pubmed.ncbi.nlm.nih.gov/18413796/
  • https://pubmed.ncbi.nlm.nih.gov/18318443/
  • https://pubmed.ncbi.nlm.nih.gov/22006998/

カスタマーフィードバック

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]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Microglia Display Heterogeneous Initial Responses to Disseminated Tumor Cells [ Cancer Res, 2025, 10.1158/0008-5472.CAN-25-3425] PubMed: 41369553
CCL26-CX3CR1 Axis Mediates a Feedback Loop between Cancer Cell and PMN-MDSCs to Promote CD8+ T Cell Exhaustion during Stomach Carcinogenesis [ Research (Wash D C), 2025, 8:1002] PubMed: 41280721
Mitochondrial-targeted photodynamic therapy combined with TGF-β inhibition potentiates anti-PD-1 therapy in pancreatic ductal adenocarcinoma [ J Nanobiotechnology, 2025, 23(1):748] PubMed: 41310702
Angiogenesis induction using organoid-tissue modules: A platform for modular vessel construction [ J Tissue Eng, 2025, 16:20417314251376104] PubMed: 41122761
GDF15-mediated enhancement of the Warburg effect sustains multiple myeloma growth via TGFβ signaling pathway [ Cancer Metab, 2025, 13(1):3] PubMed: 39871310
Negative regulation of lymphangiogenesis by Tenascin-C delays the resolution of inflammation [ iScience, 2025, 28(2):111756] PubMed: 39925433
Synergistic activity of simvastatin and irinotecan chemotherapy against glioblastoma converges on TGF-β signaling [ J Neurooncol, 2025, 174(3):621-633] PubMed: 40434539
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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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