Name: Galunisertib (LY2157299)
Brand: Selleck Chemicals
SKU: S2230
Availability: InStock
Rating: 5 (193 reviews)

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Quality Control

Batch: Purity: 99.99%

99.99

Related Targets	PKC ROCK Bcr-Abl
Other TGF-beta/Smad Products	SB431542 LDN-193189 LY2109761 LDN-193189 Dihydrochloride SIS3 Hydrochloride RepSox (E-616452) DMH1 A-83-01 Vactosertib (TEW-7197) SRI-011381 (C381)

Cell Culture, Treatment & Working Concentration

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

Solubility

In vitro
Batch:

DMSO : 74 mg/mL (200.31 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	15.000mg/ml (40.60mM)	Taking the 1 mL working solution as an example, add 50 μL of 300 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

%

% Tween 80

% ddH₂O

% DMSO

+

%

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

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.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	369.42	Formula	C₂₂H₁₉N₅O	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	700874-72-2	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CC1=NC(=CC=C1)C2=NN3CCCC3=C2C4=C5C=C(C=CC5=NC=C4)C(=O)N

Mechanism of Action

Targets/IC₅₀/Ki	TβRI (Cell-free assay) 56 nM
In vitro	Galunisertib (LY2157299) potently inhibits the TGFβ receptor signaling. It abolishes the TGFβ induced Smad2 phosphorylation in HUVEC cells, and also shows dose dependent potentiation of VEGF or bFGF induced cell proliferation in HUVEC. This compound promotes VEGF induced HUVEC cell migration and potentiates angiogenesis in the in vitro VEGF-stimulated cord formation assay. It 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. In human glioblastoma (GBM) cells, it blocks signaling through the heteromeric TGFβ receptor complex to reduce levels of active, phosphorylated SMAD.
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), with a dilution series of Galunisertib (LY2157299) 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.
In vivo	Although anti-tumor activity has been observed in several pre-clinical models, Galunisertib (LY2157299) fails to show significant in vivo angiogenic effects in the 4T1, Colo205, or A549 xenograft models. Administration of this compound ameliorates anemia in a TGF-β overexpressing transgenic mouse model of bone marrow failure. Oral administration of it at 75 mg/kg/day displays significant antitumor activity against both Calu6 and MX1 xenografts in mice. In vivo, it 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.
References	[1] http://www.google.com/patents/US7872020 [2] http://www.aacrmeetingabstracts.org/cgi/content/abstract/2006/1/59-a [3] https://pubmed.ncbi.nlm.nih.gov/21189329/ [4] http://mct.aacrjournals.org/cgi/content/short/10/11_MeetingAbstracts/C201?rss=1 [5] https://pubmed.ncbi.nlm.nih.gov/18039567/ [6] https://pubmed.ncbi.nlm.nih.gov/19706683/ [7] https://pubmed.ncbi.nlm.nih.gov/35342344/

Applications

Methods	Biomarkers	PMID
Western blot	Periostin / Fibronectin / Snail / Twist / pSmad2 / pERK / pAkt / pFAK TGF-βR1 / p-ERK	29774119
Growth inhibition assay	Cell viability	28873435
Immunofluorescence	E-cadherin	29467918

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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Galunisertib (LY2157299) TGF-beta/Smad inhibitor

Chemical Structure

Molecular Weight: 369.42