ETV1 Inhibitor, BRD32048

A cell-permeable triazine compound that directly and reversibly binds to ETS family transcription factor ETV1 (K_D = 17.1 µM) and reduces its transcriptional activity, independent of its binding to DNA. Selectively inhibits p300-dependent ETV1 acetylation at K33 and K116 and thereby promotes its degradation (~50 µM). Inhibits the invasion capacity of ETV1-dependent cell lines and primary melanocytes expressing NRAS^G12D, but not in primary melanocytes expressing NRAS. Does not affect PC3 cell line that is not dependent on ETV1 for invasion. Also it has no effect on the invasion of cancer cells expressing mutated ETV1 (K33R/K116R).

Please note that the molecular weight for this compound is batch-specific due to variable water content.

A cell-permeable triazine compound that targets the ETS family transcription factor ETV1, but not TBX21, RELA, RUNX1, RFWD2, or P/CAF, via affinity interaction (K_D = k_d/k_a = 5.853 x 10^-2 s^-1/4.128 x 10³ M^-1s^-1= 14.2 µM) and selectively suppresses ETV1-, but not MITF-, dependent reporter transcription activity in 501mel melanoma cells (2.57-fold vs 4-fold of mock level in 24 h, respectively, with or without 10 µM BRD32048) without affecting ETV1 DNA-binding activity. Shown to inhibit ETV1-dependent invasion by downregulating p300-, but not P/CAF-, mediated ETV1 lysine acetylation (K-Ac) in LNCaP & 501mel cultures (50 µM for 16 h) that are known to harbor ETV1 chromosomal rearrangement (translocation) and amplification, respectively, resulting in enhanced ETV1 degradation, while ETV1 K-Ac is not detectable in PC3 (lacking ETV1 rearrangement) & SK-MEL-28 (wild-type ETV1) cells and no invasion inhibition by BRD32048 treatment is seen in these cultures. Likewise, BRD32048 is demonstrated to inhibit invasion of NRAS^G12D-expressing primary melanocytes (pmel) only when infected to express ETV1, and no inhibition is seen in the non-infected or MYC-infected cells.

Cell permeable: yes

Primary Target
ETS family transcription factor ETV1

Reversible: yes

Packaged under inert gas

Toxicity: Standard Handling (A)

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Pop, M.S., et al. 2014. Mol. Cancer Ther.13, 1492.

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