Galunisertib (LY2157299)

製品コードS2230 バッチS223009

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₂H₁₉N₅O

分子量

369.42

CAS No.

700874-72-2

Solubility (25°C)*

体外

DMSO

300 mg/mL (812.08 mM)

Water

Insoluble

Ethanol

Insoluble

体内（毎回新しく調製した物を用意してください）

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 この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	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.

* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Galunisertib (LY2157299) is a potent TGFβ receptor I (TβRI) inhibitor with IC50 of 56 nM in a cell-free assay. Phase 2/3.
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. ^[2] 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. ^[3] In human glioblastoma (GBM) cells, it 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, this compound fails to show significant in vivo angiogenic effects in the 4T1, Colo205, or A549 xenograft models. ^[2] Administration of it ameliorates anemia in a TGF-β overexpressing transgenic mouse model of bone marrow failure. ^[3] Oral administration of Galunisertib (LY2157299) at 75 mg/kg/day displays significant antitumor activity against both Calu6 and MX1 xenografts in mice. ^[5] 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. ^[6]

製品説明

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

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. ^[2] 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. ^[3] In human glioblastoma (GBM) cells, it 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, this compound fails to show significant in vivo angiogenic effects in the 4T1, Colo205, or A549 xenograft models. ^[2]

Administration of it ameliorates anemia in a TGF-β overexpressing transgenic mouse model of bone marrow failure. ^[3]

Oral administration of Galunisertib (LY2157299) at 75 mg/kg/day displays significant antitumor activity against both Calu6 and MX1 xenografts in mice. ^[5]

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. ^[6]

プロトコル(参考用のみ)

キナーゼアッセイ	TGF-β Type I (RIT204D) Receptors reaction
キナーゼアッセイ	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. They are incubated at 30 °C for 1 hour, then stopped and quantitated using standard TCA/BSA precipitation onto Millipore FB glass fiber filter plates and by liquid scintillation counting on a MicroBeta JET.
細胞アッセイ	細胞株	CAFs
	濃度	10 uM
	反応時間	24 h
	実験の流れ	CRC CAFs were treated with or without Galunisertib (LY2157299) (10 uM) in a medium containing U-13C-Stearic acid for 24h.
動物実験	動物モデル	Nude mice implanted subcutaneously with Calu6 or MX1 cells
	投薬量	75 mg/kg/day
	投与方法	Orally

参考

http://www.google.com/patents/US7872020
http://www.aacrmeetingabstracts.org/cgi/content/abstract/2006/1/59-a
https://pubmed.ncbi.nlm.nih.gov/21189329/

http://mct.aacrjournals.org/cgi/content/short/10/11_MeetingAbstracts/C201?rss=1
https://pubmed.ncbi.nlm.nih.gov/18039567/
https://pubmed.ncbi.nlm.nih.gov/19706683/
https://pubmed.ncbi.nlm.nih.gov/35342344/

+ 展开

カスタマーフィードバック

: Data from [Lab Chip, 2013, 13(10), 1969-78]

: Data from [Data independently produced by , , Cancer Research, 2014, 74(21): 5963-77 ]

: Data from [Data independently produced by , , Clin Cancer Res, 2018, doi:10.1158/1078-0432.CCR-18-1346]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

NADPH oxidase 1/4 dual inhibition impairs transforming growth factor-beta protumorigenic effects in cholangiocarcinoma cancer-associated fibroblasts [ Signal Transduct Target Ther, 2025, 10(1):257]	PubMed: 40820091
TGF-β inhibition restores hematopoiesis and immune balance via bone marrow EPCs in aplastic anemia [ Exp Mol Med, 2025, 57(6):1324-1338]	PubMed: 40588527
WISP3 upregulates SDCBP expression to promote the progression of non-small cell lung cancer via the TGF-β signaling pathway [ Biochem Pharmacol, 2025, 240:117082]	PubMed: 40571215
Morin Reactivates Nrf2 by Targeting Inhibition of Keap1 to Alleviate Deoxynivalenol-Induced Intestinal Oxidative Damage [ Int J Mol Sci, 2025, 26(3)1086]	PubMed: 39940854
Synergistic activity of simvastatin and irinotecan chemotherapy against glioblastoma converges on TGF-β signaling [ J Neurooncol, 2025, 174(3):621-633]	PubMed: 40434539
Hypoxia-induced histone methylation and NF-κB activation in pancreas cancer fibroblasts promote EMT-supportive growth factor secretion [ bioRxiv, 2025, 2025.01.30.635486]	PubMed: 39974981
Fibrotic response to anti-CSF-1R therapy potentiates glioblastoma recurrence [ Cancer Cell, 2024, 42(9):1507-1527.e11]	PubMed: 39255775
Cellular origin and clonal evolution of human dedifferentiated liposarcoma [ Nat Commun, 2024, 15(1):7941]	PubMed: 39266532
TGF-β signalling limits effector function capacity of NK cell anti-tumour immunity in human bladder cancer [ EBioMedicine, 2024, 104:105176]	PubMed: 38810560
Logic-based mechanistic machine learning on high-content images reveals how drugs differentially regulate cardiac fibroblasts [ Proc Natl Acad Sci U S A, 2024, 121(5):e2303513121]	PubMed: 38266046

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。