LY2157299
LY2157299 (CAS 700874-72-2) is a small-molecule antagonist that selectively targets the transforming growth factor-beta type I receptor (TβRI). By blocking signaling through TβRI, it prevents phosphorylation of downstream effectors Smad2 and Smad3, thereby interfering with the TGF-β signaling pathway. Preclinical studies indicate LY2157299 inhibits β1-integrin activation, reduces tumor cell invasion, lowers connective tissue growth factor (CTGF) production, and suppresses angiogenesis. Currently in phase II clinical trials, LY2157299 is being investigated primarily for therapeutic potential against hepatocellular carcinoma and glioblastoma.
- 1. Talha Ijaz. "Fibroblasts: Key Cells in Inflammation and Fibrosis." University of Texas Medical Branch.May, 2018.
- 2. Ijaz T, Jamaluddin M, et al. "Coordinate activities of BRD4 and CDK9 in the transcriptional elongation complex are required for TGFβ-induced Nox4 expression and myofibroblast transdifferentiation." Cell Death Dis. 2017 Feb 9;8(2):e2606. PMID:28182006
| 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. |
| Cell experiment: [1] | |
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Cell lines |
HLE and HLF cells |
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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. |
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Reaction Conditions |
100 nM, 16 hours |
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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] | |
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Animal models |
Nude mice implanted with Calu6 or MX1 cells |
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Dosage form |
Oral administration, 75mg/kg, twice a day |
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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. |
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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. |
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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. |
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| Description | LY2157299 is a potent inhibitor of TGFβ receptor I (TβRI) with IC50 of 56 nM. | |||||
| Targets | TβRI | |||||
| IC50 | 56 nM | |||||
Quality Control & MSDS
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Chemical structure
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