EG01377 dihydrochloride

• CAT Number: I045838
• CAS Number: 2749438-61-5
• Molecular Formula: C26H32Cl2N6O6S2
• Molecular Weight: 659.60
• Purity: ≥95%
• Synonyms: (2S)-2-[[3-[[5-[4-(aminomethyl)phenyl]-2,3-dihydro-1-benzofuran-7-yl]sulfonylamino]thiophene-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoic acid;dihydrochloride
• InChI: InChI=1S/C26H30N6O6S2.2ClH/c27-14-15-3-5-16(6-4-15)18-12-17-7-10-38-22(17)21(13-18)40(36,37)32-19-8-11-39-23(19)24(33)31-20(25(34)35)2-1-9-30-26(28)29;;/h3-6,8,11-13,20,32H,1-2,7,9-10,14,27H2,(H,31,33)(H,34,35)(H4,28,29,30);2*1H/t20-;;/m0../s1
• InChIKey: ZYFLTIBQQSYBQT-FJSYBICCSA-N
• SMILES: C1COC2=C1C=C(C=C2S(=O)(=O)NC3=C(SC=C3)C(=O)NC(CCCN=C(N)N)C(=O)O)C4=CC=C(C=C4)CN.Cl.Cl

EG01377 dihydrochloride is a potent, bioavailable and selective inhibitor of neuropilin-1 (NRP1), with a Kd of 1.32 μM, and IC50s of 609 nM for both NRP1-a1 and NRP1-b1. EG01377 dihydrochloride has antiangiogenic, antimigratory, and antitumor effects[1].
EG01377 (3-30 μM; 30 minutes) inhibits vascular endothelial growth factor A (VEGF-A) stimulated tyrosine phosphorylation of VEGF-R2/KDR[1].
EG01377 (30 μM) is able to significantly reduce HUVEC cell migration in response to VEGFA[1].
EG01377 (30 μM; 5 days) can delay the VEGF-induced wound closure[1].
EG01377 (30 μM) reduces network area, length, and branching points[1].
EG01377 (30 μM; 7 days) reduces VEGF-induced angiogenesis[1].
EG01377 (30 μM; 7 days) in combination with VEGFA reduces A375P (malignant melanoma) spheroid outgrowth[1].
EG01377 (500 nM; 2 hours) blocks the production of transforming growth factor beta (TGFβ) by Nrp1+ regulatory T-cell SMAD3/AKT (Tregs) in the presence of tumor cell-derived factors[1].
EG01377 (2 mg/kg; i.v.) exhibits an encouraging half-life of 4.29 h, sufficient to sustain once per day dosing in mice[1].

Reference

[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.
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