Palomid 529 (SG 00529) has been used in trials studying the treatment of Age-Related Macular Degeneration.

Palomid 529抑制肿瘤生长,血管生成和血管通透性.在兔视网膜脱离模型中,Palomid 529可有效抑制Müller细胞增殖,神经胶质瘢痕形成和感光细胞死亡.Palomid 529剂量依赖性抑制Ad-VEGF-A驱动的血管生成,裸鼠灌胃Palomid 529可抑制C6V10胶质瘤生长.与对照组相比,Palomid 529处理PC-3肿瘤小鼠可减少57.1%的肿瘤生长.Palomid 529明显抑制小鼠Brca1缺失肿瘤生长模型中Akt和 mTOR信号通路.

Palomid529不仅降低缺血性视网膜的增殖,而且能改善血管形成的组织和结构。Palomid 529抑制VEGF介导和bFGF介导的内皮细胞增殖,IC 50分别为20 nM 和30 nM。Palomid 529可诱导内皮细胞凋亡,降低血管内皮生长因子VEGF-A诱导的pAktS473,pGSK3βS9和pS6磷酸化。在肺癌NCI- 60细胞系中,Palomid 529显示高效的抗增殖活性,GI50< 35 μM。此外,Palomid 529可显著增强辐射对前列腺癌细胞（PC-3）的抗增殖作用。Palomid 529对PC-3细胞产生浓度依赖性生长抑制。Palomid 529抑制PC-3中辐射诱导的p-Akt激活,并降低Bcl-2/Bax的比例。

Estrogen receptor binding assays: The proteins are produced with rabbit reticulocyte lysates. The amount of template used in each reaction is determined empirically and expression is monitored in parallel reactions where [35S]methionine is incorporated into the receptor followed by gel electrophoresis and exposure to film. Binding reactions of the estrogen receptors (ER) and Palomid 529 are carried out in 100 mL final volumes in TEG buffer [10 mM Tris (pH 7.5), 1.5 mM EDTA, 10% glycerol]. In vitro transcribed-translated receptor (5 μL) is used in each binding reaction in the presence of 0.5 nM [3H]estradiol (E2). Palomid 529 is routinely tested from 10?11 to 10?6 M and diluted in ethanol. The reactions are incubated at 4 °C overnight and bound E2 is quantified by adding 200 mL dextran-coated charcoal. After a 15-minutes rotation at 4 °C, the tubes are centrifuged for 10 minutes and 150 mL of the supernatant are added to 5 mL scintillation mixture for determination of cpm by liquid scintillation counting. The maximum binding is determined by competing bound E2 with only the ethanol vehicle. Controls for background are included in each experiment using 5 mL unprogrammed rabbit reticulocyte lysate. This value, typically 10% to 15% of the maximal counts, is subtracted from all values. The data are plotted and Ki values are calculated. Experiments are conducted at least thrice in duplicate.

Human umbilical vascular endothelial cells (HUVEC) are used. The proliferation assay is carried out by seeding the HUVECs in 96-well plates at a density of 1,000 per well in complete medium. Following a 24-hour plating period, the cells are starved for 24 hours in 0.5% serum before being treated with Palomid 529 in the presence of 10 ng/mL basic fibroblast growth factor (bFGF) or VEGF in complete medium. After 48 hours, cell number is determined using a colorimetric method. The results are expressed as the percentage of the maximal bFGF or VEGF response in the absence of Palomid 529. Nonproliferating endothelial cells are assayed by growing HUVECs to quiescence in 96-well plates and treating with Palomid 529 for 48 hours. Initially, 5,000 cells per well are seeded and confluence is achieved the next day. The plates are incubated for another 24 hours to ensure growth arrest before treatment with Palomid 529. (Only for Reference)