ENPP1 Inhibitor C is a selective inhibitor of Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) with an IC50 value of 10µM [1]. ENPP1 Inhibitor C exhibited an IC50 of 2.3µM with cGAMP and 70µM with ATP[1]. ENPP1 Inhibitor C has been used to regulate the cGAS/STING pathway and to synthesize novel fluorescent probes[2].
In vitro, ENPP1 Inhibitor C pretreatment at 300nM for 2h effectively activated STING signaling and stimulated type I IFN responses in THP-1 cells[3].
In vivo, ENPP1 Inhibitor C treatment via subcutaneous injection at a dose of 100mg/kg/day for 21 days significantly inhibited 4T1 tumor growth, resulting in a significant reduction in the number of pulmonary metastatic nodules and intraperitoneal nodules in the murine tumor model[3].
References:
[1] Kumar M, Lowery R G. Development of a high-throughput assay to identify inhibitors of ENPP1[J]. SLAS DISCOVERY: Advancing the Science of Drug Discovery, 2021, 26(5): 740-746.
[2] Kawaguchi M, Han X, Hisada T, et al. Development of an ENPP1 fluorescence probe for inhibitor screening, cellular imaging, and prognostic assessment of malignant breast cancer[J]. Journal of medicinal chemistry, 2019, 62(20): 9254-9269.
[3] Sun Y, Chen M, Han Y, et al. Discovery of Pyrido [2, 3-d] pyrimidin-7-one derivatives as highly potent and efficacious ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) inhibitors for cancer treatment[J]. Journal of Medicinal Chemistry, 2024, 67(5): 3986-4006.
ENPP1 Inhibitor C是一种选择性外核苷酸焦磷酸酶/磷酸二酯酶1（ENPP1）抑制剂，对ENPP1的IC50值为10µM[1]。ENPP1 Inhibitor C对cGAMP和ATP的IC50值分别为2.3µM和70µM[1]。ENPP1 Inhibitor C已被用于调控cGAS/STING通路及新型荧光探针的合成研究[2]。
在体外，300nM浓度的ENPP1 Inhibitor C预处理2小时可有效激活THP-1细胞中的STING信号通路并刺激I型干扰素反应[3]。
在体内，皮下注射ENPP1 Inhibitor C（100mg/kg/day）连续21天能显著抑制小鼠肿瘤模型中的4T1肿瘤生长，并明显减少肺转移结节和腹腔结节数量[3]。