MAZ51 is a selective vascular endothelial growth factor receptor 3 (VEGFR-3; FLT4) tyrosine kinase inhibitor[1]. MAZ51 is an indolinone-based molecule that inhibits the proliferation of human endothelial cells and tumor cells and induces apoptosis[2]. MAZ51 can aggravate cisplatin nephrotoxicity[3].
In vitro, pretreatment of human prostate cancer PC-3 cells with MAZ51 (3μM) for 4h inhibited vascular endothelial growth factor C (VEGF-C)-induced vascular endothelial growth factor receptor 3 (VEGFR-3) phosphorylation and blocked serine/threonine kinase (Akt) phosphorylation[4]. MAZ51 (2.5-5μM) for 24h in two glioma cell lines (rat C6 and human U251MG cells) induced morphological changes in glioma cell lines and induced G2/M cell cycle arrest[5].
In vivo, MAZ51 (8mg/kg) was intraperitoneally injected into rats bearing mammary tumor MT450 cell xenografts, which significantly inhibited tumor growth and reduced the number of proliferating cell nuclear antigen (PCNA)-positive cells[6]. MAZ51 (10mg/kg) was subcutaneously injected into mice with full-thickness skin lesions, which may have affected lymphangiogenesis but not angiogenesis[7].
References:
[1] Varney M L, Singh R K. VEGF-C-VEGFR3/Flt4 axis regulates mammary tumor growth and metastasis in an autocrine manner[J]. American journal of cancer research, 2015, 5(2): 616.
[2] Hlophe Y N, Joubert A M. Vascular endothelial growth factor‐C in activating vascular endothelial growth factor receptor‐3 and chemokine receptor‐4 in melanoma adhesion[J]. Journal of Cellular and Molecular Medicine, 2022, 26(23): 5743-5754.
[3] Black L M, Farrell E R, Barwinska D, et al. VEGFR3 tyrosine kinase inhibition aggravates cisplatin nephrotoxicity[J]. American Journal of Physiology-Renal Physiology, 2021, 321(6): F675-F688.
[4] Yamamura A, Nayeem M J, Muramatsu H, et al. MAZ51 blocks the tumor growth of prostate cancer by inhibiting vascular endothelial growth factor receptor 3[J]. Frontiers in Pharmacology, 2021, 12: 667474.
[5] 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.
[6] 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.
[7] Takada K, Nakajima Y, Urai T, et al. Effects of inhibition of lymphangiogenesis by the vascular endothelial growth factor receptor 3 (VEGFR-3) inhibitor, MAZ51 on full thickness wounds in mice[J]. Veins and Lymphatics, 2021, 10(1).
MAZ51是一种选择性血管内皮生长因子受体3（VEGFR-3；FLT4）酪氨酸激酶抑制剂[1]。MAZ51是一种基于吲哚酮的分子，能够抑制人类内皮细胞和肿瘤细胞的增殖，并诱导细胞凋亡[2]。MAZ51会加重顺铂肾毒性[3]。
在体外，MAZ51（3μM）预处理人前列腺癌PC-3细胞4h，抑制了血管内皮生长因子C（VEGF-C）诱导的血管内皮生长因子受体3（VEGFR-3）磷酸化，阻断了丝氨酸/苏氨酸激酶（Akt）磷酸化[4]。MAZ51（2.5-5μM）两种胶质瘤细胞系（大鼠C6和人U251MG细胞）24h，诱导了胶质瘤细胞系的形态变化，诱导了G2/M期细胞周期停滞[5]。
在体内，MAZ51（8mg/kg）通过腹腔注射治疗乳腺肿瘤MT450细胞异种移植大鼠，显著抑制了肿瘤的生长，减少了增殖细胞核抗原（PCNA）阳性细胞的数量[6]。MAZ51（10mg/kg）通过皮下注射治疗全层皮肤损伤小鼠，可能影响了淋巴管生成，但不会影响血管生成[7]。