LY-2109761 is an orally-bioavailable pyrrolopyrazole inhibitor of the TGF-b1/2 kinase subtypes in Phase I and II clinical studies for malignant malignancies. With Ki potencies of 38 nM and 300 nM, respectively, LY-2109761 has been studied in metastatic pancreatic cancer cells and completely inhibits basal and TGF-b1-stimulated migration and invasion of L3.6pl/GLT cells. [1] LY-2109761 treatment suppresses Smad2 phosphorylation and the Smad-dependent downstream pathway. [2]

LY-2109761 is synergistic with gemcitabine, significantly prolonging survival times and reducing tumor volume and metastatic events. [1] Additionally, LY2109761 enhances radiation response and prolongs survival in glioblastomas. Prolliferation assays displayed a reduction of NMA-23 cell viability and inhibited self-renewal of glioblastoma cancer stem-like cells (CSLC). [3]