POM 1 is a nucleoside triphosphate diphosphohydrolase (NTPDase) inhibitor with Ki values of 2.58μM, 3.26μM and 28.8μM for NTPDase1 (CD39), NTPDase3 and NTPDase2, respectively[1]. POM 1 can inhibit ATP decomposition, but also blocks central synaptic transmission, an effect that is independent of NTPDase inhibition[2]. POM 1 is an inorganic compound that can be used to make heavy liquids and is widely used for density separation[3].
In vitro, POM 1 (100μM) treatment of macrophages for 24h inhibited intracellular ectonucleotidase activity, inhibited the increase in intracellular free Ca2+ caused by nucleotides, inhibited ATP-induced P2X7-related cell pyroptosis, and inhibited LPS-induced NO production[4]. POM 1 (5μM) treatment of H1299 and A549 cells for 24h significantly increased lipid peroxide levels and increased the expression of ferroptosis-related proteins[5].
In vivo, intraperitoneal injection of POM 1 (5mg/kg) in multiple myeloma (MM) model mice significantly reduced spleen weight and the number of tumor cells in the spleen[6]. Intraperitoneal injection of POM 1 (250μg) in CD39-deficient and wild-type mice significantly increased the number of natural killer (NK) cells and enhanced effector function[7].
References:
[1] Müller C E, Iqbal J, Baqi Y, et al. Polyoxometalates—a new class of potent ecto-nucleoside triphosphate diphosphohydrolase (NTPDase) inhibitors[J]. Bioorganic & medicinal chemistry letters, 2006, 16(23): 5943-5947.
[2] Wall M J, Wigmore G, Lopatář J, et al. The novel NTPDase inhibitor sodium polyoxotungstate (POM-1) inhibits ATP breakdown but also blocks central synaptic transmission, an action independent of NTPDase inhibition[J]. Neuropharmacology, 2008, 55(7): 1251-1258.
[3] Savage N M. The use of sodium polytungstate for conodont separations[J]. Journal of Micropalaeontology, 1988, 7(1): 39-40.
[4] Pimenta-dos-Reis G, Torres E J L, Quintana P G, et al. POM-1 inhibits P2 receptors and exhibits anti-inflammatory effects in macrophages[J]. Purinergic Signalling, 2017, 13: 611-627.
[5] Lin J W, Zhou Y, Xiao H P, et al. Antitumor effects of a Sb-rich polyoxometalate on non-small-cell lung cancer by inducing ferroptosis and apoptosis[J]. Chemical Science, 2024, 15(37): 15367-15376.
[6] Yang R, Elsaadi S, Misund K, et al. Conversion of ATP to adenosine by CD39 and CD73 in multiple myeloma can be successfully targeted together with adenosine receptor A2A blockade[J]. Journal for immunotherapy of cancer, 2020, 8(1).
[7] Zhang H, Vijayan D, Li X Y, et al. The role of NK cells and CD39 in the immunological control of tumor metastases[J]. Oncoimmunology, 2019, 8(6): e1593809.
POM 1是一种核苷三磷酸二磷酸水解酶（NTPDase）抑制剂，对NTPDase1（CD39）、NTPDase3和NTPDase2的Ki值分别为2.58μM、3.26μM和28.8μM[1]。POM 1能够抑制ATP分解，但也会阻断中枢突触传递，这种作用与NTPDase抑制无关[2]。POM 1是一种无机化合物，能够用于制造重质液体，广泛用于密度分离[3]。
在体外，POM 1（100μM）处理巨噬细胞24h，抑制了细胞内的外核苷酸酶活性，抑制了核苷酸引起的细胞内的游离Ca2+增加，抑制了ATP诱导的P2X7相关细胞焦亡，抑制了LPS诱导的NO产生[4]。POM 1（5μM）处理H1299和A549细胞24h，显著升高了脂质过氧化物水平，增加了铁死亡相关蛋白的表达[5]。
在体内，POM 1（5mg/kg）通过腹腔注射处理多发性骨髓瘤（MM）模型小鼠，显著减轻了脾脏重量，减少了脾脏中的肿瘤细胞数量[6]。POM 1（250μg）通过腹腔注射治疗CD39缺陷型和野生型小鼠，显著增加了自然杀伤（NK）细胞数量，增强了效应功能[7]。