LY364947

LY364947 is a selective inhibitor of the TGFβ/Activin/NODAL pathway that inhibits ALK5 (IC₅₀ = 59 nM)(Sawyer et al.). LY364947 less effectively inhibits TGFβRII (IC₅₀ = 400 nM), p38 MAPK (IC₅₀ = 740 nM), and mixed lineage kinase-7 (MLK-7; IC₅₀ = 1,400 nM) (Li et al., 2006; Sawyer et al.).

REPROGRAMMING

• In combination with valproic acid, can replace SOX2 in reprogramming of mouse embryonic fibroblasts transduced with OCT4, KLF4 and c-MYC (Ichida et al.).

DIFFERENTIATION

• Blocks chondrogenesis induced by mechanical load in human mesenchymal stem cells (Li et al., 2010).
• Restores the hematopoietic potential of mouse para-aortic splanchnopleural cells deficient for the Evi-1 transcription factor (Sato et al.).
• Impairs definitive endoderm differentiation competence in human embryonic stem (ES) cells (Jaremko et al.).
• Blocks TGF-β-induced endothelial-to-mesenchymal transition of NMuMg mammary epithelial cells or mouse ES cell-derived endothelial cells (Peng et al.; Kokudo et al.).

CANCER RESEARCH

• Suppresses colony-forming ability of mouse and human leukemia-initiating cells cultured with OP-9 stromal cells, and, when combined with imatinib, reduces lethality in a mouse model of chronic myeloid leukemia (Naka et al.).
• Reduces invasiveness of MDA-MB-231 breast cancer cells in a matrigel invasion assay (Shiou et al.).