SML2238

NAV-2729

≥98% (HPLC)

• Synonym(s): 3-(4-Chlorophenyl)-5-(4-nitrophenyl)-2-(phenylmethyl)-pyrazolo[1,5-a]pyrimidin-7(4H)-one, NAV 2729, NAV2729
• Empirical Formula (Hill Notation): C₂₅H₁₇ClN₄O₃
• CAS Number: 419547-11-8
• Molecular Weight: 456.88
• UNSPSC Code: 12352200
• NACRES: NA.77
• MDL number: MFCD01455625
• Assay: ≥98% (HPLC)
• Form: powder

Properties

• assay: ≥98% (HPLC)
• form: powder
• color: white to beige
• solubility: DMSO: 2 mg/mL, clear
• storage temp.: 2-8°C
• SMILES string: O=C1C=C(C2=CC=C([N+]([O-])=O)C=C2)NC3=C(C4=CC=C(Cl)C=C4)C(CC5=CC=CC=C5)=NN31
• InChI: 1S/C25H17ClN4O3/c26-19-10-6-18(7-11-19)24-22(14-16-4-2-1-3-5-16)28-29-23(31)15-21(27-25(24)29)17-8-12-20(13-9-17)30(32)33/h1-13,15,27H,14H2
• InChI key: GUUWHOSUKOCRHG-UHFFFAOYSA-N

Description

Biochem/physiol Actions

Inhibitor against ArfGEF ARNO- and BRAG2/GEP100-dependent ARF1/6 activity. Inhibits melanoma growth in vitro and in vivo.

NAV-2729 (IC50 of 1.5 μM) has a therapeutic benefit in reducing the adverse effect of diabetic retinopathy in animal models.

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.).

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable