LY2157299 (Synonyms: LY-2157299;LY 2157299)

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 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.