DFP00173 is an aquaporin-3 (AQP3) inhibitor that inhibits mouse and human AQP3 with an IC50 value of approximately 0.1-0.4μM, exhibiting antitumor activity[1, 2]. DFP00173 effectively inhibits intracellular H2O2 uptake[3].
In vitro, treatment of multiple myeloma cell lines (RPMI8226, KMS-11, U266, KMS-27) with DFP00173 (1μM) for 1-6 days significantly reduced the survival rate of all four cell lines, but did not significantly increase the rate of apoptosis, and inhibited cellular mitochondrial respiration[4]. Treatment of HCT8 cells with DFP00173 (5μM) for 45min reduced cell viability and glycerol uptake[5].
In vivo, DFP00173 (20mg/kg) administered via intradiscal injection for 5 weeks in a rat model of intervertebral disc degeneration (IVDD) induced by annular puncture (AFP) restored the intervertebral disc space in IVDD rats[6].
References:
[1] Sonntag Y, Gena P, Maggio A, et al. Identification and characterization of potent and selective aquaporin-3 and aquaporin-7 inhibitors[J]. Journal of Biological Chemistry, 2019, 294(18): 7377-7387.
[2] Pimpão C, da Silva I V, Soveral G. The expanding role of aquaporin-1, aquaporin-3 and aquaporin-5 as transceptors: Involvement in cancer development and potential druggability[J]. International Journal of Molecular Sciences, 2025, 26(3): 1330.
[3] Mu K, Kitts D D. Application of a HyPer-3 sensor to monitor intracellular H2O2 generation induced by phenolic acids in differentiated Caco-2 cells[J]. Analytical Biochemistry, 2022, 659: 114934.
[4] Tanaka M, Yasui M, Hara-Chikuma M. Aquaporin 3 inhibition suppresses the mitochondrial respiration rate and viability of multiple myeloma cells[J]. Biochemical and Biophysical Research Communications, 2023, 676: 158-164.
[5] Angelini I, Centrone M, Caponio G R, et al. MOMAST® Downregulates AQP3 Expression and Function in Human Colon Cells[J]. Antioxidants, 2024, 14(1): 26.
[6] Sang Y, Zhao H, Wu J, et al. Downregulation of aquaporin 3 promotes hyperosmolarity-induced apoptosis of nucleus pulposus cells through PI3K/Akt/mTOR pathway suppression[J]. arXiv preprint arXiv:2507.02231, 2025.
DFP00173是一种水通道蛋白3（aquaporin-3，AQP3）抑制剂，抑制小鼠和人 AQP3，IC50值约为0.1-0.4μM，具有抗肿瘤活性[1, 2]。DFP00173能够有效抑制细胞内H2O2的摄取[3]。
在体外，DFP00173（1µM）处理多发性骨髓瘤细胞系（RPMI8226, KMS-11, U266, KMS-27）1-6天，均显著降低了4种细胞的存活数量，但并未显著提高细胞凋亡率，抑制了细胞线粒体呼吸作用[4]。DFP00173（5µM）处理HCT8细胞45min，降低了细胞活力和甘油摄取率[5]。
在体内，DFP00173（20mg/kg）通过椎间盘内注射治疗椎间盘穿刺（AFP）诱导的椎间盘退变（IVDD）大鼠模型5周，恢复了IVDD大鼠的椎间盘间隙[6]。