Background:

MAZ51 is originally synthesized as a selective inhibitor for VEGFR-3. VEGFR-3, a receptor tyrosine kinase (RTK), shows restricted expression in the adult organism and is virtually exclusively expressed on the lymphatic endothelium.VEGFR-3 activation is involved in inducing lymphangiogenesis. Inhibition of VEGFR-3 activation can suppress metastasis formation [1].

In vitro: MAZ51 caused dramatic shape changes, including the retraction of cellular protrusions and cell rounding in the rat C6 and human U251MG glioma cell lines. MAZ51 also inhibited cellular proliferation by inducing G2/M phase cell cycle arrest without triggering significant cell death in dose- and time-dependent patterns. Treatment of glioma cells with MAZ51 increased phosphorylated GSK3β levels by activating Akt and increasing levels of active RhoA. Treatment with MAZ51 in VEGFR-3-silenced cells caused the alterations of cell shape and cytoskeletal arrangements [1]. MAZ51 surprisingly blocked proliferation of human dermal microvascular endothelial cells (HDMEC) with an IC50 of< 1 μM [2].

In vivo: In the rats subcutaneously injected with MT450 rat mammary carcinoma cells, treatment daily with MAZ51 (8 mg/kg, i.p.) significantly suppressed the growth of MT450 tumors when compared with the solvent-treated animals [2]. In the mammary fat pad of BALB/c mice injected with the metastatic mammary tumor cell line Cl66, MAZ51 treatment (i.p.) significantly inhibited tumor growth in a dose-dependent manner [3].

参考文献:
[1].  Park J H, Shin Y J, Riew T R, et al. The indolinone MAZ51 induces cell rounding and G2/M cell cycle arrest in glioma cells without the inhibition of VEGFR-3 phosphorylation: involvement of the RhoA and Akt/GSK3β signaling pathways[J]. PloS one, 2014, 9(9): e109055.
[2].  Kirkin V, Thiele W, Baumann P, et al. MAZ51, an indolinone that inhibits endothelial cell and tumor cell growth in vitro, suppresses tumor growth in vivo[J]. International journal of cancer, 2004, 112(6): 986-993.
[3].  Michelle L. Varney, Anguraj Sadanandam, Joyce C. Solheim, James E. Talmadge and Rakesh K. Singh Experimental and Molecular Therapeutics 28: Antibodies and Therapeutic Targets VEGFR3 antagonist (MAZ51) directly and indirectly inhibits murine mammary tumor growth and metastasis.