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[1].
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) [1].NAZ2329 (25 µM; 0-90 min) obviously promotes the phosphorylation level of paxillin at Tyr-118 site, leading to inhibition for PTPR substrate[1]. Cell Proliferation Assay[1] Cell Line: Rat glioblastoma cells bearing C6 clone, human U251 glioblastoma cells
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[1]. Animal Model: Female BALB/c- nu/nu mice aged 4 week-old bearing parental or Ptprz-knockdown C6 cells[1]
[1]. Akihiro Fujikawa, et al. Targeting PTPRZ inhibits stem cell-like properties and tumorigenicity in glioblastoma cells. Sci Rep. 2017 Jul 17;7(1):5609.