Antibodies
LY2157299
- 貨號 Cat. No.
- S2230
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
LY2157299
Catalog No.S22301 Product Citations
LY2157299 is a potent TGFβ receptor I (TβRI) inhibitor with IC50 of 56 nM. Phase 2.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | LY2157299 is a potent TGFβ receptor I (TβRI) inhibitor with IC50 of 56 nM. Phase 2. | |||||
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| Targets | TβRI | |||||
| IC50 | 56 nM [1] | |||||
| In vitro | LY2157299 potently inhibits the TGFβ receptor signaling. LY2157299 abolishes the TGFβ induced Smad2 phosphorylation in HUVEC cells. LY2157299 also shows dose dependent potentiation of VEGF or bFGF induced cell proliferation in HUVEC. LY2157299 also promotes VEGF induced HUVEC cell migration. LY2157299 potentiates angiogenesis in the in vitro VEGF-stimulated cord formation assay. [2] LY2157299 inhibits TGF-β-mediated SMAD2 activation and hematopoietic suppression in primary hematopoietic stem cells in a dose-dependent manner. LY2157199 treatment stimulates hematopoiesis from primary MDS bone marrow specimens. [3] In human glioblastoma (GBM) cells, LY2157299 treatment blocks signaling through the heteromeric TGFβ receptor complex to reduce levels of active, phosphorylated SMAD. [4] | |||||
| In vivo | Although anti-tumor activity has been observed in several pre-clinical models, LY2157299 fails to show significant in vivo angiogenic effects in the 4T1, Colo205, or A549 xenograft models. [2] Administration of LY2157299 ameliorates anemia in a TGF-β overexpressing transgenic mouse model of bone marrow failure.[3] Oral administration of LY2157299 at 75 mg/kg/day displays significant antitumor activity against both Calu6 and MX1 xenografts in mice. [5] In vivo, LY2157299 induces angiogenesis and enhances VEGF and basic-fibroblast-growth-factor-induced angiogenesis in a Matrigel-plug assay, whereas adding an alpha5-integrin-neutralizing antibody to the Matrigel selectively inhibits this enhanced response. [6] | |||||
| Features | ||||||
Protocol(Only for Reference)
Kinase Assay: [1]
| TGF-β Type I (RIT204D) Receptors reaction | Reactions: 170-200 nM enzyme in 1 × KB (50 mM Tris pH 7.5, 150 mM NaCl, 4 mM MgCl2, 1 mM NaF, 2 mM β-mercaptoethanol), LY2157299 dilution series in 1 × KB /16% DMSO (20 μM to 1 nM final concentration with 4% DMSO final concentration), reactions are started by adding ATP mix (4 μM ATP/ 1 μCi 33P-α-ATP final concentrations) in 1 × KB. Reactions are incubated at 30 °C for 1 hour. Reactions are stopped and quantitated using standard TCA/BSA precipitation onto Millipore FB glass fiber filter plates and by liquid scintillation counting on a MicroBeta JET. |
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Animal Study: [5]
| Animal Models | Nude mice implanted subcutaneously with Calu6 or MX1 cells |
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| Dosages | 75 mg/kg/day |
| Administration | Orally |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01220271 | Recruiting | Glioma | Eli Lilly and Company | 2011-04 | Phase 1|Phase 2 |
| NCT01373164 | Recruiting | Neoplasms|Neoplasm Metastasis|Pancreatic Cancer | Eli Lilly and Company | 2011-12 | Phase 1|Phase 2 |
| NCT01582269 | Recruiting | Glioblastoma | Eli Lilly and Company | 2012-04 | Phase 2 |
| NCT01722825 | Recruiting | Neoplasms|Neoplasm Metastasis | Eli Lilly and Company | 2012-11 | Phase 1 |
| NCT01746004 | Completed | Healthy Volunteers | Eli Lilly and Company | 2013-01 | Phase 1 |
Chemical Information
| Molecular Weight (MW) | 369.42 |
|---|---|
| Formula | C22H19N5O |
| CAS No. | 700874-72-2 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 74 mg/mL (200 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | <1 mg/mL (<1 mM) | ||
| * <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. | |||
| Chemical Name | 4-(2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)quinoline-6-carboxamide |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
|---|---|---|---|---|
| Mass(mg) | 0.36942 | 3.6942 | 7.3884 | 11.0826 |
Product Citations (1)
