PGMI-004A 是磷酸甘油酸变位酶 1 抑制剂，IC50=13.1 μM。

PGMI-004A is an effective inhibitor of phosphoglycerate mutase 1 (IC50: 13.1 μM).

PGMI-004A inhibits PGAM1 with an IC50 of approximately 13.1 μM and the Kd value of the PGMI-004A-PGAM1 interaction is determined to be 7.2±0.7 μM from the fluorescence-based binding assay. PGMI-004A treatment induces decreased cell proliferation of diverse human cancer and leukemia cells, but not control human dermal fibroblasts (HDF), human foreskin fibroblasts (HFF), human HaCaT keratinocyte cells and human melanocyte PIG1 cells, suggesting minimal non-specific toxicity of PGMI-004A in normal, proliferating human cells. PGMI-004A may allosterically modulate the enzyme activity of PGAM1. The Ki value is determined to be 3.91±2.50 μM using a Dixon plot analysis. The Kd value for protein-ligand interaction is calculated to be 9.4±2.0 μM. PGMI-004A (20 μM) treatment, causes significantly reduced lactate production that is rescued by methyl-2-PG treatment but has no significant effect on intracellular ATP levels. Inhibition of PGAM1 activity by PGMI-004A (20 μM) treatment results in decreased 2-PG and increased 3-PG levels in H1299 cells, which could be rescued by treatment with methyl-2-PG. PGMI-004A (20 μM) treatment results in decreased oxidative PPP flux and NADPH/NADP+ratio, as well as reduced biosynthesis of lipids and RNA, and cell proliferation in H1299 cells [1].

PGMI-004A treatment causes significantly decreased tumor growth and tumor size in treated mice compared with mice receiving vehicle control. Treatment with PGMI-004A effectively inhibits PGAM1 enzyme activity in tumors in vivo in resected tumors from xenograft nude mice. The xenograft experiment is performed by injecting H1299 cells to nude mice. Six days post-injection, mice are divided into two groups (n=8/group) and treated with either PGMI-004A (100mg/kg/day) or vehicle for 21 days [1].

1313738-90-7

C21H12F3NO6S

463.38

DMSO:125 mg/mL (269.76 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years