Phosphoglycerate mutase 1 (PGAM1) is a glycolytic enzyme that dynamically converts 3-phosphoglycerate (3PG) to 2-phosphoglycerate (2PG), which was upregulated to coordinate glycolysis, pentose phosphate pathway (PPP) and serine biosynthesis to promote cancer cell proliferation and tumor growth in a variety of cancers. However, only a few inhibitors of PGAM1 have been reported with poor molecular or cellular efficacy. In this paper, a series of xanthone derivatives were discovered as novel PGAM1 inhibitors through scaffold hopping and sulfonamide reversal strategy based on the lead compound PGMI-004A. Most xanthone derivatives showed higher potency against PGAM1 than PGMI-004A and exhibited moderate anti-proliferation activity on different cancer cell lines.

磷酸甘油酸突变酶1（PGAM1）是一种糖酵解酶，可将3-磷酸甘油酸（3PG）动态转化为2-磷酸甘油酸（2PG），后者被上调以协调糖酵解，磷酸戊糖途径（PPP）和丝氨酸生物合成，从而促进癌细胞增殖和肿瘤。各种癌症的生长。然而，据报道仅有少数PGAM1抑制剂具有较差的分子或细胞效力。本文通过基于铅化合物PGMI-004A的脚手架跳跃和磺酰胺逆转策略，发现了一系列黄嘌呤衍生物作为新型PGAM1抑制剂。大多数x吨酮衍生物比PGMI-004A对PGAM1的效力更高，并且在不同的癌细胞系中表现出中等的抗增殖活性。