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Chemical Structure| 700874-71-1 Chemical Structure| 700874-71-1

Structure of LY2109761
CAS No.: 700874-71-1

Chemical Structure| 700874-71-1

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LY2109761 demonstrates oral activity and selectivity as an inhibitor of TGF-β receptor type I/II, with Kis of 38 nM and 300 nM, respectively.

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Product Details of LY2109761

CAS No. :700874-71-1
Formula : C26H27N5O2
M.W : 441.52
SMILES Code : N1(CCOC2=CC=C3C(C4=C(CCC5)N5N=C4C6=NC=CC=C6)=CC=NC3=C2)CCOCC1
MDL No. :MFCD12923354
InChI Key :IHLVSLOZUHKNMQ-UHFFFAOYSA-N
Pubchem ID :11655119

Safety of LY2109761

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Isoform Comparison

Biological Activity

Target
  • TGFβRII

    TβRII, Ki:300 nM

  • TGFβRI/ALK5

    TβRI, Ki:38 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
Esophageal squamous cell carcinoma cells 20 μM 24 h LY2109761 reduced DJ-1-induced metastasis of bystander ESCC cells PMC9413943
U251 cells 2 mg/ml 24 h and 48 h Inhibition of TGFβ pathway, weakening the interaction between RUNX1 and p-SMAD3/SUV39H1 PMC6872557
N9 cells 2 mg/ml 24 h and 48 h Inhibition of TGFβ pathway, weakening the interaction between RUNX1 and p-SMAD3/SUV39H1 PMC6872557
CT26 cells 10 μM 25 h LY2109761 inhibits TGF-β-mediated cell migration, invasion, and tumorigenicity PMC2776056
CT26-Luc cells 10 μM 5 days LY2109761 inhibits TGF-β-mediated cell migration, invasion, and tumorigenicity PMC2776056
A549 cells 2μM 72 h To evaluate the effect of LY2109761 on TGF-β or S1P-induced epithelial-mesenchymal transition (EMT). The results showed that LY2109761 reversed the morphological changes induced by TGF-β or S1P, inhibited the up-regulation of the mesenchymal marker CD90 and the down-regulation of the epithelial marker CD326. PMC9306821
MC38 cells 5 μM 5 days LY2109761 inhibited TGF-β-induced proliferation, migration, and invasion of MC38 cells. PMC2831103
SW620 cells 5 μM 5 days LY2109761 inhibited TGF-β-induced migration and invasion of SW620 cells. PMC2831103
PANC-1 cells 5 μM 72 h To evaluate the cytotoxicity of LY2109761 on PANC-1 cells, results showed that LY2109761 did not exhibit significant cytotoxicity at low concentrations, with only minor toxicity observed at 50 μM. PMC7372733
Pancreatic stellate cells (PSCs) 5 μM 48 h To evaluate the inhibitory effect of LY2109761 on type I collagen expression in pancreatic stellate cells (PSCs), results showed that LY2109761 significantly reduced type I collagen expression. PMC7372733

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Nude mice Pulmonary metastasis model Intraperitoneal injection 50 mg/kg Once a week for 6 weeks LY2109761 significantly suppressed the invasion of K150 cells and alleviated pulmonary metastasis PMC9413943
Mice PVR mouse model Intraperitoneal injection 10 mg/kg Consecutive 14 days To investigate the inhibitory effect of LY2109761 on fibrosis induced by FXa in PVR mouse model, results showed LY2109761 significantly alleviated FXa-induced fibrosis. PMC8300057
Nude mice Patient-derived xenograft (PDX) model Tail vein injection 50 mg/kg Once every other day for 15 days Inhibition of TGFβ pathway, reducing tumor growth and invasion PMC6872557
Balb/c mice Balb/c nude mice Oral 50 mg/kg Twice daily for 23 days LY2109761 reduces liver metastasis and prolongs survival PMC2776056
BALB/c mice Asthma-like disease model Subcutaneous injection 50 mg/kg Single dose 15 minutes before To evaluate the effect of LY2109761 on S1P-induced asthma-like features. The results showed that LY2109761 inhibited S1P-induced airway hyperresponsiveness (AHR), mucus hyperproduction, and pulmonary fibrosis, and reversed S1P-induced CD90 up-regulation and CD326 down-regulation. PMC9306821
C57BL/6 mice Colorectal cancer liver metastasis model Oral 50 mg/kg Twice daily for 28 days LY2109761 significantly inhibited the metastasis of colorectal cancer cells to the liver and prolonged the survival of mice. PMC2831103
Mice miR-424(322)/503 double-knockout mice Oral 50 mg/kg Twice daily for 24 hours To inhibit TGF-β signaling and observe its effect on mammary gland involution. Results showed that LY2109761 treatment inhibited involution, maintaining the structure of secretory acini and increasing epithelial density. PMC4015488
Nude mice Orthotopic pancreatic cancer model Intravenous injection 13.2 mg/kg Every 5 days for a total of 6 injections To evaluate the antitumor efficacy of LY2109761 in an orthotopic pancreatic cancer model, results showed that LY2109761 significantly inhibited tumor growth and reduced collagen expression and activation of PSCs in the tumor. PMC7372733

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.26mL

0.45mL

0.23mL

11.32mL

2.26mL

1.13mL

22.65mL

4.53mL

2.26mL

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