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LY2157299

LY2157299

Catalog No.

A8348

TGF-βR1 inhibitor,potent and selective

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Grouped product items
Size	Price	Stock
10mM (in 1mL DMSO)	$66.00	In stock
Evaluation Sample	$30.00	In stock
5mg	$55.00	In stock
10mg	$77.00	In stock
50mg	$165.00	In stock

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Background
Product Citation
Chemical Properties
Protocol
Biological Activity
Quality Control

Background

LY2157299 is a potent small-molecule antagonist that specifically inhibits Transforming Growth Factor-β receptor I (TβRI). LY2157299 is now under phase II clinical evaluation of its anti-carcinoma activity against hepatocellular carcinoma and glioblastoma¹.

LY2157299 has been shown to inhibit β1-integrin activation and block the invasion and migration of hepatocellular cancer cells. In addition, multiple studies have revealed LY2157299 blocked the CTGF production and inhibited neoangiogenesis resulting suppression of hepatocellular carcinoma growth¹.

LY2157299 has been reported to decrease phosphorylated Smad2 and Smad3 expression and inhibit the tumor growth in both human anaplastic carcinoma lung cell (Calu6) or human carcinoma breast cell (MX1) xenografted nude mice².

References:
1.?Giannelli G1, Villa E, Lahn M.Transforming Growth Factor-β as a Therapeutic Target in Hepatocellular Carcinoma. Cancer Res. 2014 Apr 1;74(7):1890-4. doi: 10.1158/0008-5472.CAN-14-0243. Epub 2014 Mar 17.
2.?Bueno L1, de Alwis DP, Pitou C, Yingling J, Lahn M, Glatt S, Trocóniz IFSemi-mechanistic modelling of the tumour growth inhibitory effects of LY2157299, a new type I receptor TGF-beta kinase antagonist, in mice. Eur J Cancer. 2008 Jan;44(1):142-50.

Product Citation

Chemical Properties

Storage	Store at -20°C
M.Wt	369.42
Cas No.	700874-72-2
Formula	C₂₂H₁₉N₅O
Synonyms	LY-2157299;LY 2157299
Solubility	insoluble in H2O; ≥18.45 mg/mL in DMSO; ≥26.15 mg/mL in EtOH
Chemical Name	4-[2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]quinoline-6-carboxamide
SDF	Download SDF
Canonical SMILES	CC1=CC=CC(=N1)C2=NN3CCCC3=C2C4=C5C=C(C=CC5=NC=C4)C(=O)N
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment: [1]
Cell lines	HLE and HLF cells
Preparation method	The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.
Reaction Conditions	100 nM, 16 hours
Applications	HLE and HLF cells were allowed to migrate for 16 hours on fibronectin, vitronectin, laminin-5 and fibrinogen in the presence of increasing concentrations (1 nM, 10 nM and 100 nM) of LY2157299. LY2157299 significantly inhibited HLE and HLF migration on different ECM substrates. When testing the inhibition of Smad phosphorylation, two different HCC cell lines were pretreated for 16 hours with 100 nM of LY2157299 and then stimulated with 2 ng of TGF-β1 for 30 min. LY2157299 inhibited de novo phosphorylation of p-SMAD2 at the same efficiency in HLE and HLF after stimulation with TGF-β1. Besides that, increased expression of E-cadherin was observed in HLE and HLF cells after treatment for 48 hours.
Animal experiment: [2]
Animal models	Nude mice implanted with Calu6 or MX1 cells
Dosage form	Oral administration, 75mg/kg, twice a day
Applications	LY2157299 induced a 70% decrease in phosphorylated Smad (pSmad) for both types of cell lines. The time at which pSmad recovered 80% of baseline was approximately 6 h after administration.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1] Dituri F, Mazzocca A, Peidrò F J, et al. Differential inhibition of the TGF-β signaling pathway in HCC cells using the small molecule inhibitor LY2157299 and the D10 monoclonal antibody against TGF-β receptor type II. PloS one, 2013, 8(6): e67109. [2] Bueno L, de Alwis D P, Pitou C, et al. Semi-mechanistic modelling of the tumour growth inhibitory effects of LY2157299, a new type I receptor TGF-β kinase antagonist, in mice. European journal of cancer, 2008, 44(1): 142-150.