Home TGF-beta/Smad TGF-beta/Smad inhibitor Galunisertib (LY2157299) For research use only.

Galunisertib (LY2157299)

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

Galunisertib (LY2157299) Chemical Structure

Galunisertib (LY2157299) Chemical Structure

CAS No. 700874-72-2

Purity & Quality Control

Galunisertib (LY2157299) Related Products

Signaling Pathway

TGF-beta/Smad Signaling Pathways

TGF-beta/Smad Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Panc-1 Function Assay 10 μM 48 h DMSO stimulates the cell invasion into the collagen gel and the Matrigel-coated collagen gel 24780821
Sf9 Function assay Inhibition of human recombinant GST-fused ALK5 expressed in Sf9 insect cells using casein as substrate by proprietary radioisotopic protein kinase assay, IC50 = 0.0694 μM. 26483198
Sf9 Function assay Inhibition of human ALK5 expressed in Sf9 insect cells using casein as substrate in presence of [gamma-33P]ATP, IC50 = 0.051 μM. 28135685
Sf9 Function assay 1 hr Inhibition of human His-tagged TGFbetaR1 T204D mutant expressed in Sf9 insect cells after 1 hr by HTRF assay, IC50 = 0.0041 μM. 29422332
B16 Antitumor assay 75 mg/kg Antitumor activity against mouse B16 cells in mouse assessed as inhibition of tumor growth at 75 mg/kg, po bid relative to vehicle-treated control 24786585
B16 Antitumor assay 75 mg/kg Antitumor activity against mouse B16 cells in mouse assessed as suppression of tumor volume at 75 mg/kg, po bid relative to vehicle-treated control 24786585
B16 Antitumor assay 75 mg/kg Antitumor activity against mouse B16 cells in mouse assessed as inhibition of lymph node metastasis at 75 mg/kg, po bid relative to vehicle-treated control 24786585
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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)
56 nM
In vitro
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]
Kinase Assay 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.
Cell Research Cell lines CAFs
Concentrations 10 uM
Incubation Time 24 h
Method

CRC CAFs were treated with or without Galunisertib (10 uM) in a medium containing U-13C-Stearic acid for 24h.
Experimental Result Images Methods Biomarkers Images PMID
Western blot TGF-βR1 / p-ERK Periostin / Fibronectin / Snail / Twist / pSmad2 / pERK / pAkt / pFAK 30881035
Growth inhibition assay Cell viability 28873435
Immunofluorescence E-cadherin 29467918
In Vivo
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]
Animal Research Animal Models Nude mice implanted subcutaneously with Calu6 or MX1 cells
Dosages 75 mg/kg/day
Administration Orally
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04031872 Unknown status
Colorectal Cancer Metastatic
The Netherlands Cancer Institute|Vall d''Hebron Institute of Oncology|Agendia|European Organisation for Research and Treatment of Cancer - EORTC|Azienda Ospedaliera Niguarda Cà Granda|Fundación para la Investigación del Hospital Clínico de Valencia|University of Campania Luigi Vanvitelli|University of Turin Italy|Eli Lilly and Company|Catalan Institute of Health|Universitaire Ziekenhuizen KU Leuven
 February 2020 Phase 1|Phase 2
NCT03470350 Withdrawn
Colorectal Cancer Metastatic
The Netherlands Cancer Institute|Vall d''Hebron Institute of Oncology|Agendia|European Organisation for Research and Treatment of Cancer - EORTC|Azienda Ospedaliera Niguarda Cà Granda|Fundación para la Investigación del Hospital Clínico de Valencia|University of Campania Luigi Vanvitelli|University of Turin Italy|Eli Lilly and Company|Catalan Institute of Health|Universitaire Ziekenhuizen KU Leuven
 August 24 2018 Phase 1|Phase 2
NCT02734160 Completed
Metastatic Pancreatic Cancer
Eli Lilly and Company|AstraZeneca
 June 15 2016 Phase 1
NCT02452008 Recruiting
Prostate Cancer
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|Eli Lilly and Company
 May 3 2016 Phase 2
NCT02752919 Completed
Healthy
Eli Lilly and Company
 April 2016 Phase 1

Chemical Information & Solubility

Molecular Weight 369.42 Formula

C22H19N5O
CAS No. 700874-72-2 SDF Download Galunisertib (LY2157299) SDF
Smiles CC1=NC(=CC=C1)C2=NN3CCCC3=C2C4=C5C=C(C=CC5=NC=C4)C(=O)N
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 74 mg/mL ( (200.31 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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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.

Handling Instructions

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