| Description | 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. |
| In vitro | NAV-2729(25 μM)能够约15%地抑制Δ13Arf6的自发核苷酸交换。NAV-2729还能通过25%抑制Δ13Arf6被BRAG2Sec7PH激活。Δ17Arf1没有可测量的自发核苷酸交换。NAV-2729抑制Δ17Arf1被BRAG2Sec7PH激活的效率显著高于Arf6（50%）。在剂量-反应实验中，10 μM NAV-2729能使Δ17Arf1的核苷酸交换率降低50%，而即便是在25 μM NAV-2729的作用下，Δ13Arf6的50%抑制也未能实现。NAV-2729阻断ARNO和GEP100介导的Arf6上的鸟嘌呤核苷酸交换以及Arf6的自发激活和其通过cytohesins和BRAG的激活。用NAV-2729处理葡萄膜黑色素瘤细胞可以干扰细胞的非依赖性生长。相比Arf6，NAV-2729对Arf1的效果更佳。 |
| In vivo | 在同种异位移植的小鼠眼脉络膜黑色素瘤模型中，NAV-2729干扰了肿瘤的发生和肿瘤的生长[2]。 |
| molecular weight | 456.88 |
| Molecular formula | C25H17ClN4O3 |
| CAS | 419547-11-8 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility | DMSO: 6.88 mg/mL (15.05 mM), Sonication is recommended. |
| References | 1. Benabdi S, et al. Family-wide Analysis of the Inhibition of Arf Guanine Nucleotide Exchange Factors with Small Molecules: Evidence of Unique Inhibitory Profiles. Biochemistry. 2017 Sep 26;56(38):5125-5133. 2. Yamauchi Y, et al. Machineries regulating the activity of the small GTPase Arf6 in cancer cells are potential targets for developing innovative anti-cancer drugs. Adv Biol Regul. 2017 Jan;63:115-121. |