LY2109761

製品コードS2704 バッチS270402

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 2 mg/mL (4.52 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
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 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 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]

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 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.
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.

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：

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
Connexin 43 controls metastatic behavior in triple negative breast cancer through TGFβ1-Smad3-intergin αV signaling axis Based on optical image diagnosis [ SLAS Technol, 2024, 29(5):100190] PubMed: 39299505
TGF-β signaling promotes cervical cancer metastasis via CDR1as [ Mol Cancer, 2023, 22(1):66] PubMed: 37004067
Bromodomain-containing protein 4 activates androgen receptor transcription and promotes ovarian fibrosis in PCOS [ Cell Rep, 2023, 42(9):113090] PubMed: 37669164
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
FUT1-mediated terminal fucosylation acts as a new target to attenuate renal fibrosis [ Mol Med, 2023, 29(1):55] PubMed: 37085770

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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