LY2109761

貨號 Cat. No.: S2704
規格 Size: 5~200mg
品牌 Brand: Selleckchem

Description

LY2109761

Catalog No.S27041 Product Citations

LY2109761 is a novel selective TGF-β receptor type I/II (TβRI/II) dual inhibitor with K_i of 38 nM and 300 nM, respectively; shown to negatively affect the phosphorylation of Smad2.

Size

Price

Stock

Quantity

10mM/1mLIn DMSO	USD 544	In stock	0 1 2 3 4 5 6 7 8 9 10
5mg	USD 340	In stock	0 1 2 3 4 5 6 7 8 9 10
10mg	USD 466	In stock	0 1 2 3 4 5 6 7 8 9 10
50mg	USD 1348	In stock	0 1 2 3 4 5 6 7 8 9 10
200mg	USD 3112	In stock	0 1 2 3 4 5 6 7 8 9 10

Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw

Biological Activity

Description	LY2109761 is a novel selective TGF-β receptor type I/II (TβRI/II) dual inhibitor with K_i of 38 nM and 300 nM, respectively; shown to negatively affect the phosphorylation of Smad2.
Targets	TβRI	TβRII
IC50	38 nM (K_i)	300 nM (K_i) ^[1]
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]
Features

Protocol(Only for 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.
Solubility	0.5% CMC/0.25% Tween 80, 16 mg/mL

References

Chemical Information

Download LY2109761 SDF

Molecular Weight (MW)	441.52
Formula	C₂₆H₂₇N₅O₂
CAS No.	700874-71-1

Storage	3 years -20â„ƒPowder
Storage	6 months-80â„ƒin DMSO
Syonnyms	N/A

Solubility (25°C) *	In vitro	DMSO	2 mg/mL (4 mM)
		Water	<1 mg/mL (<1 mM)
		Ethanol	<1 mg/mL (<1 mM)
	In vivo	0.5% CMC/0.25% Tween 80,	16 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.