| Bioactivity | AT-533 is a potent Hsp90 and HSV inhibitor. AT-533 suppresses tumor growth and angiogenesis by blocking the HIF-1α/VEGF/VEGFR-2 signaling pathway. AT-533 also inhibits the activation of the downstream pathways, including Akt/mTOR/p70S6K, Erk1/2 and FAK. AT-533 inhibits the tube formation, cell migration, and invasion of human umbilical vein endothelial cells (HUVECs)[1][2][3]. | ||||||||||||
| Invitro | AT-533 (0-1350 nM; 24 h 或 48 h) 抑制 20ng/mL VEGF 诱导的管形成、细胞迁移和 HUVEC侵袭[1]。AT-533 (2 μM 或 75 μM; 24 h) 抑制缺氧诱导的乳腺癌细胞中 HIF-1α/VEGF 信号通路，抑制 Akt/mTOR/p70S6K, Erk1/2 和 FAK 磷酸化[1]。AT-533 (10 nM, 50 nM; 48 h) 对绒毛膜 (CAM) 模型具有抗血管生成能力[1]。AT-533 (0.5 μM; 2 h, 4 h) 降低 RAW264.7 和 BV2 细胞受 HSV-1 诱导引起 TNF-α、IL-1β 和 IL-6 的产生[2]。 Cell Viability Assay[1] Cell Line: | ||||||||||||
| In Vivo | AT-533 (10 mg/kg; 腹腔注射; 每天 1 次，共 21 天) 抑制小鼠 MDA-MB-231 乳腺癌异种移植瘤模型中 HIF-1α/VEGF 信号通路相关蛋白的表达[1]。AT-533 (1, 2, 4 mg/kg; 腹腔注射; 每天 1 次，共 30 天) 在 Sprague-Dawley 大鼠的亚急性毒性试验中，不引起死亡、食欲下降、体重下降、不良反应[3]。 Animal Model: | ||||||||||||
| Name | AT-533 | ||||||||||||
| CAS | 908112-37-8 | ||||||||||||
| Formula | C23H30N4O3 | ||||||||||||
| Molar Mass | 410.51 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Zhang PC, et al. AT-533, a novel Hsp90 inhibitor, inhibits breast cancer growth and HIF-1α/VEGF/VEGFR-2-mediated angiogenesis in vitro and in vivo. Biochem Pharmacol. 2020 Feb;172:113771. [2]. Li F, et al. AT-533, a Hsp90 inhibitor, attenuates HSV-1-induced inflammation. Biochem Pharmacol. 2019 Aug;166:82-92. [3]. Wu Y, et al. Subacute toxicological evaluation of AT-533 and AT-533 gel in Sprague-Dawley rats. Exp Ther Med. 2021 Jun;21(6):632. |