10-甲基褐海蛇毒素1（10MA-1），是一种简化的类似物质，对蛋白激酶C（PKC）同工酶具有高结合亲和力，并且具有最小的肿瘤促进和促炎活性。最近的研究表明，10MA-1能够在体外重新激活潜伏的人类免疫缺陷病毒（HIV），作为HIV根除策略的一部分。然而，由于10MA-1的极限溶解度引起了剂量限制，进一步的体内研究已被放弃。为了解决这个问题，我们合成了10MA-1的磷酸酯衍生物，18-O-磷酸酯-10-甲基褐海蛇毒素1（phos-10MA-1），以提高其在体内研究中的水溶性。我们在体外研究了phos-10MA-1的溶解度、PKC结合亲和力和生物活性，并且其生物活性与10MA-1相当。此外，我们还进行了体内药代动力学研究，结果表明未来需要进一步优化以提高其代谢稳定性。© 2023 The Author(s). 由日本生物科学、生物技术和农业化学学会代表牛津大学出版。

10-Methyl-aplog-1 (10MA-1), a simplified analogue of aplysiatoxin, exhibits a high binding affinity for protein kinase C (PKC) isozymes with minimal tumor-promoting and proinflammatory activities. A recent study suggests that 10MA-1 could reactivate latent human immunodeficiency virus (HIV) in vitro for HIV eradication strategy. However, further in vivo studies were abandoned by a dose limit caused by the minimal water solubility of 10MA-1. To overcome this problem, we synthesized a phosphate ester of 10MA-1, 18-O-phospho-10-methyl-aplog-1 (phos-10MA-1) to improve water solubility for in vivo studies. The solubility, PKC binding affinity, and biological activity of phos-10MA-1 were examined in vitro, and the biological activity was comparable with 10MA-1. The pharmacokinetics studies in vivo were also examined and suggest that further optimization for improving metabolic stability is required in the future.© The Author(s) 2023. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.