TP-472

Research use only, not for human use.

TP-472 is a novel BRD9/7 chemical probe that has excellent potency (BRD9 KD=33nM; BRD7 KD=340 nM by ITC).

TP-472 is a novel BRD9/7 chemical probe that has excellent potency (BRD9 KD=33nM; BRD7 KD=340 nM by ITC), >30 fold selectivity over all other bromodomain family members except BRD7 and is cell active (EC50 320 nM in a BRD9 NanoBRET assay); has a good PK profile and is suitable for in vivo applications.

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.Cell Viability Assay Cell 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 Assay Cell Line:M14 and SKMEL-28 cells Concentration: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 Analysis Cell Line:A375 cells Concentration:10 μM Incubation Time:24 h Result:Resulted in the upregulation of pro-apoptotic genes.

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. 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.

TP472

Chromatin/Epigenetic

Bromodomain

Bromodomain

——

——

2079895-62-6

333.391

C20H19N3O2

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (299.96 mM)

CC1=C(C=C(C=C1)C(=O)NC2CC2)C3=C4N=CC=CN4C(=C3)C(=O)C

3-(6-acetylpyrrolo[1,2-a]pyrimidin-8-yl)-N-cyclopropyl-4-methylbenzamide

(-20℃)

With Ice Pack

≥ 2 years