Galunisertib (LY2157299)

Catalog No.S2230 Batch:S223008

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Technical Data

Formula

C22H19N5O
Molecular Weight 369.42 CAS No. 700874-72-2
Solubility (25°C)* In vitro DMSO 73 mg/mL (197.6 mM)
Water Insoluble
Ethanol Insoluble
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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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

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]
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]

Protocol (from 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.
Cell Assay:

[7]
  • 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.
Animal Study:

[5]
  • Animal Models

    Nude mice implanted subcutaneously with Calu6 or MX1 cells

  • Dosages

    75 mg/kg/day

  • Administration

    Orally

Customer Product Validation

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]

Data from [Data independently produced by , , Sci Rep, 2016, 6:23056.]

Selleck's Galunisertib (LY2157299) has been cited by 191 publications

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
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
TGF-β signalling limits effector function capacity of NK cell anti-tumour immunity in human bladder cancer [ EBioMedicine, 2024, 104:105176] PubMed: 38810560
Alterations of ceramide synthesis induce PD-L1 internalization and signaling to regulate tumor metastasis and immunotherapy response [ Cell Rep, 2024, 43(8):114532] PubMed: 39046874
Blockade of TGF-β and PD-L1 by bintrafusp alfa promotes survival in preclinical ovarian cancer models by promoting T effector and NK cell responses [ Br J Cancer, 2024, 10.1038/s41416-024-02677-9] PubMed: 38622286
GPA33 expression in colorectal cancer can be induced by WNT inhibition and targeted by cellular therapy [ Oncogene, 2024, ] PubMed: 39472498
CCL3 predicts exceptional response to TGFβ inhibition in basal-like pancreatic cancer enriched in LIF-producing macrophages [ NPJ Precis Oncol, 2024, 8(1):246] PubMed: 39478186
Galunisertib downregulates mutant type I collagen expression and promotes MSCs osteogenesis in pediatric osteogenesis imperfecta [ Biomed Pharmacother, 2024, 175:116725] PubMed: 38744219
CDCA5 promoted cell invasion and migration by activating TGF-β1 pathway in human ovarian cancer cells [ J Ovarian Res, 2024, 17(1):68] PubMed: 38539247

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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