SU1498 (AG 1498) is a potent inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), with an IC50 value of 0.7μM [1]. SU1498 can inhibit alveolar formation and regulate capillary number in neonatal mice by inhibiting vascular endothelial growth factor receptor[2]. SU1498 has been widely used to inhibit mitochondrial energy production to regulate cancer cell viability[3].
In vitro, SU1498 treatment for 48h inhibited the growth of DU145 cells with an IC50 value of 2.19 ± 0.14μM[4]. Treatment of MS-1 cells with 5μg/ml SU1498 for 24h blocked VEGFR-2 signaling, resulting in a decrease in Ets-1 levels[5]. Treatment of U87 cells with 10µM SU1498 for 72 hours inhibited cell proliferation, induced an increase in the number of apoptotic cells and altered cell morphology[6].
In vivo, SU1498 treatment (1μg/μl; 1μg in 1μl DMSO) via intravitreal injection for 7 days can inhibit laser-induced ocular angiogenesis in mice[7]. One month after subcutaneous injection of a single dose of SU1498 (30mg/kg) into the back of newborn mice, the development of renal tubules and glomerular was abnormal, accompanied by glomerular malformation, tubular dilation, and cell degeneration[8].
References:
[1] Boguslawski G, McGlynn P W, Harvey K A, et al. SU1498, an inhibitor of vascular endothelial growth factor receptor 2, causes accumulation of phosphorylated ERK kinases and inhibits their activity in vivo and in vitro[J]. Journal of Biological Chemistry, 2004, 279(7): 5716-5724.
[2] SJ C, CS G, JM S, et al. Su1498 Inhibits Alveolarization in Newborn Mice[J]. Pediatric Research, 2004, 56(4): 667-667.
[3] Kam Y, Winer L, Romero N. Screening of kinase inhibitors as bioenergetic metabolism modulator using the XF Real-Time ATP Rate Assay[J]. Cancer Research, 2023, 83(7_Supplement): 3969-3969.
[4] Kisielewska J, Ligeza J, Klein A. The effect of tyrosine kinase inhibitors, tyrphostins: AG1024 and SU1498, on autocrine growth of prostate cancer cells (DU145)[J]. Folia histochemica et cytobiologica, 2008, 46(2): 185-191.
[5] Arbiser J L, Larsson H, Claesson-Welsh L, et al. Overexpression of VEGF 121 in immortalized endothelial cells causes conversion to slowly growing angiosarcoma and high level expression of the VEGF receptors VEGFR-1 and VEGFR-2 in vivo[J]. The American journal of pathology, 2000, 156(4): 1469-1476.
[6] Mesti T, Savarin P, Triba M N, et al. Metabolic impact of anti-angiogenic agents on U87 glioma cells[J]. PloS one, 2014, 9(6): e99198.
[7] Shu-Ya T, Qiu-Yang Z, Jing-Jing L, et al. Suppression of pathological ocular neovascularization by a small molecule, SU1498[J]. Biomedicine & Pharmacotherapy, 2020, 128: 110248.
[8] Lee S J, Cho S J, Ju S Y, et al. Effect of retinoic acid on renal development in newborn mice treated with an angiogenesis inhibitor[J]. Pediatrics International, 2010, 52(3): 386-392.
SU1498 (AG 1498)是一种有效的血管内皮生长因子受体2（VEGFR-2）抑制剂，IC50值为0.7μM[1]。SU1498可通过抑制血管内皮生长因子受体，来抑制新生小鼠的肺泡形成并调节毛细血管数量[2]。SU1498已被广泛应用于通过抑制线粒体能量产生来调节癌细胞活力[3]。
在体外，使用SU1498处理DU145细胞48小时可抑制其生长，IC50值为2.19 ± 0.14μM[4]。用5μg/ml的SU1498处理MS-1细胞24小时，可阻断VEGFR-2信号传导，导致Ets-1水平降低[5]。用10µM的SU1498处理U87细胞72小时，能抑制细胞增殖、诱导凋亡细胞数量增加并改变细胞形态 [6]。
在体内，通过玻璃体内注射SU1498（1μg/μl；1μg溶于1μl DMSO）处理小鼠7天，可抑制激光诱导的眼部血管生成[7]。在新出生小鼠背部单次皮下注射SU1498（30mg/kg）一个月导致肾小管和肾小球的发育出现异常，并伴有肾小球畸形、肾小管扩张和细胞变性[8]。