NRPa-308 is a potent and orally active Neuropilin-1 (NRP-1) antagonist with an IC50 of 42 μM for inhibiting VEGF-A 165 binding to NRP-1. NRPa-308 blocks the specific interaction between VEGF-A 165 and NRP-1. NRPa-308 effectively suppresses angiogenesis in vitro and in vivo and reduces the viability of a broad spectrum of human solid and haematological cancer cells. NRPa-308 inhibits tumor growth and prolongs median survival in a human breast cancer xenograft mouse model. NRPa-308 can be used for the research of multiple human malignancies including solid tumors and hematological cancers [1].
In Vivo, NRPa-308 (compound 2a) (50 mg/kg; oral gavage; every three days; 20 days) increases median mouse survival by 20%, reduces tumour growth, disrupts tumour angiogenesis, and shows no acute toxicity in a human MDA-MB-231 breast cancer xenograft model[1].
In Vitro, NRPa-308 (compound 2a) (10-42 μM; 1-2 h) inhibits VEGF-A165 binding to purified NRP-1 protein with an IC50 of 42 μM, and achieves 32% inhibition at a concentration of 10 μM[1]. NRPa-308 (0.2 μM; 72 h) reduces adhesion of HUVEC with an IC50 of 0.2 μM[1]. NRPa-308 (72 h) inhibits adhesion and viability of HUVEC (IC50 = 0.2 μM) as well as adhesion of MDA-MB-231 human breast cancer cells (IC50 = 0.5 μM)[1]. NRPa-308 (72 h) reduces viability of native, Shcontrol-modified, and ShVEGF-R2-modified MDA-MB-231 human breast cancer cells with IC50 values of 0.6 μM, 0.8 μM, and 0.9 μM respectively, but loses potency (IC50 = 9.0 μM) on ShNRP-1-modified MDA-MB-231 cells following 72 h of treatment[1]. NRPa-308 (24-72 h) reduces viability of most tested human solid and haematological cancer cell lines with IC50 values ranging from 0.10 μM to 0.60 μM after 72 h treatment, shows weaker potency against normal human fibroblasts and lymphatic endothelial cells (IC50 = 20.8 μM and 11.2 μM respectively), and exhibits no effect (IC50 ≥ 10 μM) on select solid and haematological cancer cell lines[1]. NRPa-308 (0.2 μM; 24 h) dramatically inhibits tubule formation and significantly reduces the migratory speed of VEGF-A165-stimulated HUVEC and MDA-MB-231 human breast cancer cells following 24 h of incubation[1].
References:
[1]. Liu WQ, et al. NRPa-308, a new neuropilin-1 antagonist, exerts in vitro anti-angiogenic and anti-proliferative effects and in vivo anti-cancer effects in a mouse xenograft model. Cancer Lett. 2018;414:88-98.
In Vivo, NRPa-308 (compound 2a) (50 mg/kg; oral gavage; every three days; 20 days) increases median mouse survival by 20%, reduces tumour growth, disrupts tumour angiogenesis, and shows no acute toxicity in a human MDA-MB-231 breast cancer xenograft model[1].
In Vitro, NRPa-308 (compound 2a) (10-42 μM; 1-2 h) inhibits VEGF-A165 binding to purified NRP-1 protein with an IC50 of 42 μM, and achieves 32% inhibition at a concentration of 10 μM[1]. NRPa-308 (0.2 μM; 72 h) reduces adhesion of HUVEC with an IC50 of 0.2 μM[1]. NRPa-308 (72 h) inhibits adhesion and viability of HUVEC (IC50 = 0.2 μM) as well as adhesion of MDA-MB-231 human breast cancer cells (IC50 = 0.5 μM)[1]. NRPa-308 (72 h) reduces viability of native, Shcontrol-modified, and ShVEGF-R2-modified MDA-MB-231 human breast cancer cells with IC50 values of 0.6 μM, 0.8 μM, and 0.9 μM respectively, but loses potency (IC50 = 9.0 μM) on ShNRP-1-modified MDA-MB-231 cells following 72 h of treatment[1]. NRPa-308 (24-72 h) reduces viability of most tested human solid and haematological cancer cell lines with IC50 values ranging from 0.10 μM to 0.60 μM after 72 h treatment, shows weaker potency against normal human fibroblasts and lymphatic endothelial cells (IC50 = 20.8 μM and 11.2 μM respectively), and exhibits no effect (IC50 ≥ 10 μM) on select solid and haematological cancer cell lines[1]. NRPa-308 (0.2 μM; 24 h) dramatically inhibits tubule formation and significantly reduces the migratory speed of VEGF-A165-stimulated HUVEC and MDA-MB-231 human breast cancer cells following 24 h of incubation[1].
References:
[1]. Liu WQ, et al. NRPa-308, a new neuropilin-1 antagonist, exerts in vitro anti-angiogenic and anti-proliferative effects and in vivo anti-cancer effects in a mouse xenograft model. Cancer Lett. 2018;414:88-98.