Galunisertib (LY2157299)

Catalog No.S2230

Galunisertib (LY2157299) is a potent TGFβ receptor I (TβRI) inhibitor with IC50 of 56 nM in a cell-free assay. Phase 2/3.

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Galunisertib (LY2157299) Chemical Structure

Galunisertib (LY2157299) Chemical Structure
Molecular Weight: 369.42

Validation & Quality Control

2 customer reviews :

Quality Control & MSDS

Related Compound Libraries

Galunisertib (LY2157299) is available in the following compound libraries:

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Product Information

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Product Description

Biological Activity

Description Galunisertib (LY2157299) is a potent TGFβ receptor I (TβRI) inhibitor with IC50 of 56 nM in a cell-free assay. Phase 2/3.
Targets TβRI [1]
(Cell-free assay)
IC50 56 nM
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]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
Panc-1NFmxXIJHfW6ldHnvckBCe3OjeR?=NUn2XFB4OTBizszNMnrWOFghcA>?M33mT2ROW09?MWDzeIlufWyjdHXzJJRp\SClZXzsJIlvfmG|aX;uJIlvfG9idHjlJINwdGyjZ3XuJIdmdCCjbnSgeIhmKE2jdILp[4VtNWOxYYTl[EBkd2yuYXflckBo\Wx?MYmyOFc5ODh{MR?=

... Click to View More Cell Line Experimental Data

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.

Animal Study: [5]

Animal Models Nude mice implanted subcutaneously with Calu6 or MX1 cells
Formulation Dissolved in DMSO and diluted in saline
Dosages 75 mg/kg/day
Administration Orally

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Mundla SR, Patent, 2006, US7872020.

[2] Yingling JM, et al. Proc Am Assoc Cancer Res. 2006, 47, abstract 250.

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Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-07-23)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02734160 Not yet recruiting Metastatic Pancreatic Cancer Eli Lilly and Company|AstraZeneca June 2016 Phase 1
NCT02688712 Not yet recruiting Rectal Adenocarcinoma Providence Health & Services|Eli Lilly and Company June 2016 Phase 2
NCT02452008 Recruiting Prostate Cancer Sidney Kimmel Comprehensive Cancer Center April 2016 Phase 2
NCT02752919 Completed Healthy Eli Lilly and Company April 2016 Phase 1
NCT02672475 Recruiting Estrogen Receptor Negative|HER2/Neu Negative|Progesterone Receptor Negative|Recurrent Breast Carcinoma|Stage IV Breast Cancer|Triple-Negative Breas  ...more Estrogen Receptor Negative|HER2/Neu Negative|Progesterone Receptor Negative|Recurrent Breast Carcinoma|Stage IV Breast Cancer|Triple-Negative Breast Carcinoma Vanderbilt-Ingram Cancer Center|National Cancer Institute  ...more Vanderbilt-Ingram Cancer Center|National Cancer Institute (NCI) March 2016 Phase 1

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Chemical Information

Download Galunisertib (LY2157299) SDF
Molecular Weight (MW) 369.42
Formula

C22H19N5O

CAS No. 700874-72-2
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 74 mg/mL (200.31 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 2% DMSO+30% PEG 300+ddH2O 5mg/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.
Chemical Name 4-(2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)quinoline-6-carboxamide

Customer Product Validation(2)


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Rating
Source Cancer Research, 2014, 74(21): 5963-77 . Galunisertib (LY2157299) purchased from Selleck
Method Western Blot
Cell Lines HLE、HLF cells
Concentrations 100、500 nMol/L
Incubation Time 48 h
Results Treatment of HLE and HLF cells with TGFβRI inhibitor LY2157299 led to dose-dependent loss of GLI2 levels. These data support the conclusion that the mesenchymal phenotype of HLE and HLF cell lines is due to constitutive TGFβ signaling.

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Rating
Source Lab Chip 2013 13(10), 1969-78. Galunisertib (LY2157299) purchased from Selleck
Method 3D microtissue growth
Cell Lines 393T5 lung cancer cells
Concentrations 10 uM
Incubation Time 3 days
Results These marked differences between 2D and 3D responses to TGF-β and LY2157299.The TGFβR1/TGFβR2 inhibitor, LY2157299, in that it inhibited proliferation in 2D cultures, but did not alter 3D microtissue growth.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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