NAZ2329, the first cell-permeable inhibitor of R5 subfamily of receptor-type protein tyrosine phosphatases (RPTPs), allosterically and preferentially inhibits PTPRZ (IC50=7.5 μM for hPTPRZ1) and PTPRG (IC50=4.8 μM for hPTPRG) over other PTPs. NAZ2329 binds to the active D1 domain and more potently inhibits PTPRZ-D1 fragment (IC50 of 1.1 μM) than the whole intracellular (D1?+?D2) fragment (IC50 of 7.5 μM). NAZ2329 can effectively inhibit tumor growth of the glioblastoma cells and suppress stem cell-like properties.IC50 & Target: IC50: 7.5 μM (PTPRZ), 4.8 μM (PTPRG), 35.7 μM (PTPRA), 56.7 μM (PTPRM), 23.7 μM (PTPRS), 35.4 μM (PTPRB), 15.2 μM (PTPN6), 14.5 μM (PTPN1)In Vitro: NAZ2329 (0-25 μM; 48 hours) dose-dependently inhibits cell proliferation and migration in all cell lines (rat glioblastoma cells bearing C6 clone and human U251 glioblastoma cells) .
NAZ2329 (25 μM; 0-90 min) obviously promotes the phosphorylation level of paxillin at Tyr-118 site, leading to inhibition for PTPR substrate.In Vivo: NAZ2329 (22.5 mg/kg; intraperitoneal injection; twice per week; 40 days) alone has a moderate inhibitory effect. However, the combination of Temozolomide and NAZ2329 exerts a significantly increased inhibition of tumor growth compared with the control group, the NAZ2329 monotherapy group and the Temozolomide monotherapy group.