PY-60 (C09-1164-724)

PY-60 is a robust and specific activator of YAP transcriptional activity that targets annexin A2 (ANXA2) with a K d of 1.4 µM. PY-60 directly binds to ANXA2 and antagonizes its normal cellular function of repressing YAP activity.In VitroPY-60 targets ANXA2 to activate YAP. ?/nPY-60, a thiazole-substituted derivative, dose-dependently induces luciferase activity in 293A-TEAD-LUC cells in the presence or absence of serum when cells were plated at high cell density (EC 50 =?1.5 and 1.6?μM, respectively). PY-60 treatment also dose-dependently promoted the association of YAP and TEAD proteins in cells and induced the nuclear localization of YAP in response to increased cell density. PY-60 robustly increases the levels of YAP-controlled transcripts (that is, ANRKD1 , CYR61 and CTGF ) in 293A cells and other human cell lines (that is, MCF10A, HEK293T, H69 and HaCaT), but did not augment the levels of YAP itself ( YAP1 ). ?/nPY-60 activates a proproliferative, YAP-dependent transcriptional program in the adult animal capable of remodeling the epidermis through proliferation. ?/nPY-60 liberates the ANXA2-YAP complex from the cell membrane and competes for ANXA2 binding of phosphoinositides. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoPY-60 (10?uM; applied topically to the dorsal skin of wild-type adult C57BL/6 mice over the course of 10?days) promotes a dramatic expansion of keratinocytes and K14-positive precursors, as assessed by hematoxylin and eosin and anti-K14 histological staining at the study end. PY-60 results in an approximate doubling of epidermal thickness, a result derived from an increased number of keratinocytes per unit length of skin . MCE has not independently confirmed the accuracy of these methods. They are for reference only.Form:Solid. Specifications and Purity: 98%. Molecular Formula: C16H15N3O2S. Molecular Weight: 313.37. PubChem CID: 155387479. Isomeric SMILES: C1=CC=C(C=C1)C2=CC(=NO2)C(=O)NCCCC3=NC=CS3.