TP-472

TP-472 is a selective BRD9/7 inhibitor, with K d s 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 TP-472 induces apoptosis of melanoma cells In Vitro TP-472 (1 µM, 3 µM; 24-216 hours) yields concentration-dependent growth defects in ESCs. 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: Embryonic stem cells Concentration: 1 µM, 3 µM Incubation Time: 24 hours, 72 hours, 120 hours, 168 hours, 216 hours Result: Yields concentration-dependent growth defects in ESCs. Cell Proliferation AssayCell Line: M14 and SKMEL-28 cellsConcentration: 0.1 μM, 0.5 μM, 1 μM, 2 μM, 5 μM, 10 μM Incubation Time: 24 h Result: Effectively inhibited the growth of both the BRAF mutant melanoma cell lines. Western Blot AnalysisCell Line: A375 cells Concentration: 10 μM Incubation Time: 24 h Result: Resulted in the upregulation of pro-apoptotic genes. 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: NSG mice injected with A375-MA2 cells (male five- to six-week-old)Dosage: 20 mg/kg Administration: i.p.; three times a week; for 5 weeks Result: Significantly inhibited the subcutaneous tumor growth in melanoma xenograft mouse model. Form:Solid IC50& Target:BRD9 33 nM (Kd) BRD7 0.34 μM (Kd)

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