| Description | EG01377 2HCl is a potent, bioavailable and selective inhibitor of neuropilin-1 (NRP1) with a Kd value of 1.32 μM and an IC50 value of 609 nM for both EG01377 2HCl against NRP1-a1 and NRP1-b1.EG01377 exhibits anti-angiogenic, antimigratory and antitumor activities. |
| In vitro | EG01377 2HCl (30 μM) 显著抑制由VEGFA诱导的HUVEC细胞迁移。同时，EG01377 2HCl 也减少网络区域、长度和分支点的数量。[1] 在3-30 μM浓度范围内，30分钟处理能有效抑制VEGF-A刺激的VEGF-R2/KDR酪氨酸磷酸化，其IC50为30 μM。[1] 30 μM浓度，持续5天的处理可延缓VEGF诱导的创伤闭合。[1] EG01377 2HCl 降低VEGF引起的血管生成，并且当与VEGFA结合时，能缩减A375P（恶性黑色素瘤）细胞的球体外生长。[1] 在500 nM浓度下，2小时处理阻断了存在肿瘤细胞衍生因子时，Nrp1+调节性T细胞SMAD3/AKT (Tregs)产生的转化生长因子β（TGFβ）。[1] |
| In vivo | EG0 1377 2HCl（2 mg/kg；静脉注射；BABL/c 雌性小鼠）的半衰期为4.29小时，支持小鼠每日一次的给药频率。[1] |
| Target activity | NRP1-a1 and NRP1-b:609 nM |
| Synonyms | EG01377 2HCl(2227996-00-9 Free base) |
| molecular weight | 659.6 |
| Molecular formula | C26H32Cl2N6O6S2 |
| CAS | 2749438-61-5 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 180.0 mg/mL (272.9 mM), Sonication is recommended. |
| References | 1. Powell J, et al. Small Molecule Neuropilin-1 Antagonists Combine Antiangiogenic and Antitumor Activity with Immune Modulation through Reduction of Transforming Growth Factor Beta (TGFβ) Production in Regulatory T-Cells. J Med Chem. 2018;61(9):4135-4154. 2. Klaewkla M, et al. Molecular basis of the new COVID-19 target neuropilin-1 in complex with SARS-CoV-2 S1 C-end rule peptide and small-molecule antagonists. J Mol Liq. 2021;335:116537. 3. Zhang P, et al. NRP1 promotes prostate cancer progression via modulating EGFR-dependent AKT pathway activation. Cell Death Dis. 2023;14(2):159. |