EG01377是一种神经纤毛蛋白1(neuropilin-1)拮抗剂，对NRP1-b1的Kd值为1.32μM，对NRP1-a1和NRP1-b1的IC50值均为609nM，对NRP2没有作用；EG01377具有抗血管生成，抗迁移及抗肿瘤等活性。
货号:ajcx12954
CAS:2227996-00-9
分子式:C26H30N6O6S2
分子量：586.68
溶解度:Soluble in DMSO
纯度：98%
存储：Store at -20°C
库存：现货

Background:

EG01377 is a neuropilin-1 (NRP1) antagonist, with a Kd of 1.32 μM for NRP1-b1, and IC50s of both 609 nM for NRP1-a1 and NRP1-b1, but shows no effect on NRP2; EG01377 has antiangiogenic, antimigratory, and antitumor effects.

EG01377 is a neuropilin-1 (NRP1) antagonist, with a Kd of 1.32 μM for NRP1-b1, and IC50s of both 609 nM for NRP1-a1 and NRP1-b1, but shows no effect on NRP2. EG01377 inhibits NRP1 in DU145/cells.Ad.NRP1 cells (IC50, 1.6 μM). EG01377 (3, 10, and 30 μM) inhibits VEGF-A stimulated tyrosine phosphorylation of VEGF-R2/KDR. EG01377 (30 μM) also significantly reduces HUVEC cell migration in response to VEGFA, and reduces VEGF-induced angiogenesis. Moreover, EG01377 (30 μM) in combination with VEGFA causes reduction in A375P spheroid outgrowth. EG01377 blocks the production of TGFβ by Nrp1+ Tregs in the presence of tumor cell-derived factors[1].

[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 May 10;61(9):4135-4154.

Protocol:

Kinase experiment:

The 96-well plates are precoated with NP1 protein at 3 μg/mL overnight at 4°C. On the following day, the plates are treated with blocking buffer (PBS containing 1% BSA) and washed three times with wash buffer (PBS containing 0.1% Tween-20). The various concentrations of compounds (EG01377, etc.) diluted in PBS containing 1% DMSO are added, followed by addition of 0.25 nM of bt-VEGF-A165. After 2 h of incubation at room temperature, the plates are washed three times with wash buffer. The bound bt-VEGF-A165 to NP-1 is detected by streptavidin-horseradish peroxidase conjugates and the enzyme substrate, and measured using a plate reader at A450 nm with a reference wavelength at A595 nm. Nonspecific binding is determined in the absence of NP-1 coated wells of the plates[1].

参考文献: [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 May 10;61(9):4135-4154.