Galunisertib

SKU: orb1305376

Description

Galunisertib (LY2157299) is a selective TGF-β receptor type I inhibitor (IC50=56 nM) with demonstrated antitumor activity. It is widely used in oncology research, particularly in studies exploring its mechanism in vitro and its efficacy in combination with immune checkpoint inhibitors like anti-PD-1 antibodies in vivo tumor models.

Research Area

Stem Cell & Developmental Biology

Key Properties

• CAS Number: 700874-72-2
• MW: 369.42
• Purity: 99.97%
• Formula: C₂₂H₁₉N₅O
• SMILES: Cc1cccc(n1)-c1nn2CCCc2c1-c1ccnc2ccc(cc12)C(N)=O
• Target: TGF-beta/Smad
• Solubility: DMSO:250 mg/mL (676.74 mM);Ethanol:Insoluble;10% DMSO+40% PEG300+5% Tween 80+45% Saline:6.9 mg/mL (18.68 mM)

Bioactivity

• Target IC50:
  TGFβRII:210 nM|TβRI:56 nM (cell free)|HaCaT cells:> 0.1 μM|4T1 cells:> 0.1 μM
• In Vivo:
  METHODS: To assay antitumor activity in vivo, athymic nu/nu mice bearing MX1, Calu6, or 4T1 tumors were administered Galunisertib (75 mg/kg, 10% beta-cyclodextrin-HCl) by gavage twice daily for 20-40 days. RESULTS: Galunisterib monotherapy all resulted in a significant delay in tumor growth. For MX1, Galunisertib treatment resulted in a tumor growth delay of 10.3 ± 4.3 days. For Calu6, Galunisertib treatment resulted in a tumor growth delay of 8.3 ± 2.6 days. For 4T1, Galunisertib treatment resulted in a delay in tumor growth of 13±2.4 days.
• In Vitro:
  METHODS: Mouse embryonic fibroblasts NIH3T3 were treated with Berzosertib (0.0001-10 µM) for 2 h, followed by incubation with TGFβ1 overnight, and cell proliferation was detected by 3H-thymidine proliferation assay. RESULTS: Berzosertib inhibited TGFβ1-induced proliferation with an IC50 of 0.396 µM. METHODS: Seven HCC cell lines, JHH6, SK-HEP1, SK-Suni, SK-Sora, HepG2, Hep3B, and HuH7, were treated with Galunisertib (1-10 µM) and TGF-β (5 ng/mL) for 5-24 h, and the expression levels of target proteins were detected by Western Blot. RESULTS: Addition of Galunisertib decreased p-Smad2 expression levels in all cell lines in a dose- and time-dependent manner, independent of TGF-β induction.
• Cell Research:
  Cell survival was determined using the MTT assay. The conversion of yellow water-soluble tetrazolium MTT into purple insoluble formazan is catalyzed by mitochondrial dehydrogenases and used to estimate the number of viable cells. In brief, cells were seeded in 96-well tissue culture plates at a density of 2 × 103 cells/well. After drug exposure, cells were incubated with 0.4 mg/mL MTT for 4 hours at 37°C. After incubation, the supernatant was discarded, insoluble formazan precipitates were dissolved in 0.1 mL of DMSO, and the absorbance was measured at 560 nm by use of a microplate reader. Wells with untreated cells or with drug-containing medium without cells were used as positive and negative controls respectively. For proliferation assay, MTT assay was done daily to determine the number of viable cells in untreated control and galunisertib-treated group .
• Animal Research:
  Transgenic mice expressing a fusion gene (Alb/TGF) consisting of modified porcine TGF-β1 cDNA under the control of the regulatory elements of the mouse albumin gene (26) were used under animal institute approved protocol. Mice were given LY-2157299 at a dose of 100mg/kg/day in NaCMC/SLS/PVP/antifoam solution by gastric lavage using a curved 14 G needle. Blood counts were analyzed by the Advia machine. Mice femurs were flushed and bone marrows cells were used for clonogenic assays .

Storage & Handling

• Storage: store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

LY-2157299, LY2157299, LY 2157299, inhibit, Inhibitor, Galunisertib, Smad, TGFb, TGF-b/Smad, TGFbeta/Smad, TGF-beta, TGFbeta, TβRI, Transforming growth factor beta receptors, TGFβ, TGF-β Receptor, TGF-β/Smad

Compound Identifiers

PubChem CID

10090485