TP-472 is a selective BRD9/7 inhibitor, with Kds of 33 nM and 340 nM for BRD9 and BRD7, respectively. TP-472 exhibits >30-fold selectivity for BRD9 over other bromodomain family members except BRD7[2]. TP-472 induces apoptosis of melanoma cells.IC50 & Target:Kd: 33 nM (BRD9)In Vitro:TP-472 (1 μM, 3 μM; 24-216 hours) yields concentration-dependent growth defects in ESCs[2].
TP-472 (0.1-10 μM; 24 h) effectively inhibits the growth of both the BRAF mutant melanoma cell lines at 5 and 10 μM concentrations.
TP-472 (for 2 weeks) also strongly inhibits the long-term survival of multiple melanoma cell lines (M14, SKMEL-28, A375, and A2058) at concentrations of 5 and 10 μM.
TP-472 (5-10 μM; 24 h) treatment downregulates genes encoding various extracellular matrix (ECM) proteins, including integrins, collagens, and fibronectins in A375 cells.
TP-472 (0.1-10 μM; 24 h) results in the upregulation of pro-apoptotic genes (BAX, MDM2, CDKN1A) in A375 cells.
In Vivo:TP-472 (20 mg/kg; i.p.; three times a week; for 5 weeks) significantly inhibits the subcutaneous tumor growth in melanoma xenograft mouse model.