Synonyms: 3-(4-Chlorophenyl)-5-(4-nitrophenyl)-2-(phenylmethyl)-pyrazolo[1,5-a]pyrimidin-7(4H)-one; NAV 2729; NAV2729
Molecular Formula: C25H17ClN4O3
Molecular Weight: 456.88
Linear Structural Formula: C25H17ClN4O3
MDL Number: MFCD01455625
Purity: >=98% (HPLC)
Storage: 2-8C
Biochem Physiol Actions: Originally characterized as a non-nucleotide-competitive and reversible ARF6-selective inhibitor (IC50 = 1.4 μM without GEF and 2.4 μM with 100 nM ARNO or BRAG2/GEP100) that targets ARF6 GEF-binding region, NAV-2729 prevents GEF-dependent ARF1 & ARF6 activity (% inhibition of BRAG2Sec7PH-stimulated GTPase activity/[NAV-2729] = 50% Δ17Arf1/10 μM and 15% Δ13Arf6/25 μM) with higher potency against BRAG2- than ARNO-dependent ARF1 activity (64% vs. 20% Δ17Arf1 inhibition at 25 μM in the presence of respective GEF sec7 domain). NAV-2729 treatment effectively inhibits G-alpha-q downstream signaling pathways and anchorage-independent colony growth of Mel92.1 & Mel202 melanoma cells in vitro (10 μM) as well as uveal melanoma tumor establishment in Mel202 xenograft mice in vivo (30 mg/kg/day i.p.).