NAV-2729 是有效的Arf1/Arf6活化抑制剂。

NAV-2729 inhibits six ArfGEFs (human ARNO, EFA6, BIG1, and BRAG2 and Legionella and Rickettsia RalF), the strongest effects being against BRAG2, Arf1 and Arf6.

NAV-2729(25 μM) inhibits spontaneous nucleotide exchange of Δ13Arf6 by ~15%. NAV-2729 inhibits the activation of Δ13Arf6 by BRAG2Sec7PH by 25%. Δ17Arf1 has no measurable spontaneous nucleotide exchange. Activation of Δ17Arf1 by BRAG2Sec7PH is inhibited by NAV-2729, and the efficiency is markedly higher than that for Arf6 (50%). In a dose-response experiment, nucleotide exchange rates are reduced by 50% by 10 μM NAV-2729 for Δ17Arf1 while 50% inhibition is not achieved even at 25 μM NAV-2729 for Δ13Arf6[1]. NAV-2729 blocks ARNO- and GEP100-mediated guanine nucleotide exchange on Arf6 and spontaneous activation of Arf6 and its activation by cytohesins and BRAG. The treatment of uveal melanoma cells with NAV-2729 interferes with anchorage-independent growth of the cell[1]. NAV-2729 is more effective toward Arf1 than Arf6[1].

In orthotopic xenograft mouse model of uveal melanoma, systemic treatment of NAV-2729 interfere with tumorigenesis and tumor growth[2].

419547-11-8

456.88

DMSO:50 mg/mL (109.44 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years