Axitinib (AG 013736)

Axitinib (AG 013736) is an orally active specific vascular endothelial growth factor receptor (VEGFR) inhibitor that targets VEGFR-1, VEGFR-2, and VEGFR-3 with IC₅₀ values of 0.1nM, 0.2nM, and 0.1-0.3nM, respectively^[1]. Axitinib has inhibitory effects on platelet-derived growth factor receptor (PDGFR) and tyrosine protein kinase KIT (c-KIT), with IC₅₀ values of 1.6nM and 1.7nM, respectively^[2]. Axitinib can inhibit tumor angiogenesis by inhibiting the VEGF signaling pathway, thereby inhibiting tumor growth and metastasis^[3]. Axitinib is commonly used in cancer research, especially in the treatment of renal cell carcinoma and thyroid cancer^[4].

In vitro, Axitinib (0.1-25μM) treatment of human retinal endothelial cells (HRECs) for 48h significantly increased the release of intracellular lactate dehydrogenase (LDH). Axitinib (0.1, 1μM) significantly reduced the phosphorylation of VEGFR2 in HRECs exposed to sustained high glucose concentrations and fluctuating glucose concentrations^[5].

In vivo, oral treatment of interstitial cystitis (IC) rats with Axitinib (1mg/kg/day) for 5 days reduced non-urinary contractions, increased urination interval and urine output, and alleviated urothelial exfoliation, angiogenesis, mast cell infiltration and fibrosis^[6]. Oral treatment of Renca cell xenograft mice with Axitinib (25mg/kg/day) significantly inhibited tumor growth and metastasis and promoted the infiltration and activity of CD8⁺ T cells in mice^[7].

References:
[1] Malekan M, Ebrahimzadeh M A. Vascular endothelial growth factor receptors [VEGFR] as target in breast cancer treatment: current status in preclinical and clinical studies and future directions[J]. Current Topics in Medicinal Chemistry, 2022, 22(11): 891-920.
[2] Jiang D, Xu T, Zhong L, et al. Research progress of VEGFR small molecule inhibitors in ocular neovascular diseases[J]. European Journal of Medicinal Chemistry, 2023, 257: 115535.
[3] Kelly R J, Rixe O. Axitinib—a selective inhibitor of the vascular endothelial growth factor (VEGF) receptor[J]. Targeted oncology, 2009, 4: 297-305.
[4] Keating G M. Axitinib: a review in advanced renal cell carcinoma[J]. Drugs, 2015, 75: 1903-1913.
[5] Lazzara F, Conti F, Sasmal P K, et al. Anti-angiogenic and antioxidant effects of axitinib in human retinal endothelial cells: implications in diabetic retinopathy[J]. Frontiers in Pharmacology, 2024, 15: 1415846.
[6] Shin J H, Ryu C M, Yu H Y, et al. Therapeutic effects of axitinib, an anti-angiogenic tyrosine kinase inhibitor, on interstitial cystitis[J]. Scientific Reports, 2023, 13(1): 8329.
[7] Yuan H, Cai P, Li Q, et al. Axitinib augments antitumor activity in renal cell carcinoma via STAT3-dependent reversal of myeloid-derived suppressor cell accumulation[J]. Biomedicine & Pharmacotherapy, 2014, 68(6): 751-756.

Axitinib (AG 013736)是一种具有口服活性的特异性血管内皮生长因子受体（VEGFR）抑制剂，主要靶向VEGFR-1、VEGFR-2和VEGFR-3，IC₅₀值分别为 0.1nM、0.2nM和0.1-0.3nM^[1]。Axitinib对血小板衍生生长因子受体（PDGFR） 和酪氨酸蛋白激酶KIT（c-KIT）具有抑制作用，IC₅₀值分别为1.6nM和1.7nM^[2]。Axitinib能够通过抑制VEGF信号通路，阻断肿瘤血管生成，从而抑制肿瘤生长和转移^[3]。Axitinib通常用于癌症研究，尤其是肾细胞癌和甲状腺癌的治疗^[4]。

在体外，Axitinib（0.1-25μM）处理人类视网膜内皮细胞（HRECs）48h，显著增加了细胞内乳酸脱氢酶（LDH）的释放。Axitinib（0.1, 1μM）能够显著降低暴露于持续高葡萄糖浓度以及波动的葡萄糖浓度的HRECs中VEGFR2的磷酸化^[5]。

在体内，Axitinib（1mg/kg/day）通过口服治疗间质性膀胱炎（IC）大鼠5天，减少了非排尿收缩，增加了排尿间隔和排尿量，减轻了尿路上皮剥落、血管生成、肥大细胞浸润和纤维化^[6]。Axitinib（25mg/kg/day）通过口服治疗Renca细胞异种移植小鼠，显著抑制了肿瘤的生长和转移，促进了小鼠体内CD8⁺ T细胞的浸润和活性^[7]。