Name: Galunisertib (LY2157299)
Brand: Selleck Chemicals
SKU: S2230
Rating: 5 (171 reviews)

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

CAS: 700874-72-2

Selleck's Galunisertib (LY2157299) has been cited by 171 publications

Purity & Quality Control

Galunisertib (LY2157299) Related Products

Related Targets	ALK1 ALK2 ALK3 ALK4 TGFβRI/ALK5 ALK6 TGFβRII TGF-β Smad3 Smad4 Smad5 ALK7	Click to Expand
Related Compound Libraries	Kinase Inhibitor Library PI3K/Akt Inhibitor Library MAPK Inhibitor Library Cell Cycle compound library TGF-beta/Smad compound library	Click to Expand

Signaling Pathway

TGF-beta/Smad Signaling Pathway

Choose Selective TGF-beta/Smad Inhibitors

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
Click to View More Cell Line Experimental Data

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
Kinase Assay	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
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-01-11)
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

References

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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)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

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

Water : Insoluble

Ethanol : Insoluble

Molecular Weight Calculator

In vivo
Batch:

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In vivo Formulation Calculator

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In vivo Formulation Calculator (Clear solution)

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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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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