LY2109761

製品コードS2704 バッチS270405

化学情報

	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	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.

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 K_i 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 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]

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.

参考

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：

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
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
Neuropilin-1 mediates lung tissue-specific control of ILC2 function in type 2 immunity [ Nat Immunol, 2022, 23(2):237-250]	PubMed: 35075279
Neutrophil extracellular traps promote metastasis in gastric cancer patients with postoperative abdominal infectious complications [ Nat Commun, 2022, 13(1):1017]	PubMed: 35197446
Recruitment of LEF1 by Pontin chromatin modifier amplifies TGFBR2 transcription and activates TGFβ/SMAD signalling during gliomagenesis [ Cell Death Dis, 2022, 13(9):818]	PubMed: 36153326

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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