PGMI-004A is a potent phosphoglycerate mutase 1 ( PGAM1 ) inhibitor with an IC 50 of 13.1 μM.
Storage Temp
Store at -20°C
Shipped In
Ice chest + Ice pads
Product Description
PGMI-004A is a potent phosphoglycerate mutase 1 ( PGAM1 ) inhibitor with an IC 50 of 13.1 μM.
In Vitro
PGMI-004A inhibits PGAM1 with an IC 50 of approximately 13.1 μM and the K d value of the PGMI-004A-PGAM1 interaction is determined to be 7.2±0.7 μM from fluorescence-based binding assay. PGMI-004A may allosterically modulate the enzyme activity of PGAM1. The K i value is determined to be 3.91±2.50 μM using Dixon plot analysis. The K d value for protein-ligand interaction is calculated to be 9.4±2.0 μM. 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. Treatment with PGMI-004A (20 μM) results in significantly reduced lactate production that is rescued by methyl-2-PG treatment, but has no significant effect on intracellular ATP levels. 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. PGMI-004A treatment results in 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
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. PGMI-004A treatment results in significantly decreased tumor growth and tumor size in treated mice compared with mice receiving vehicle control. Moreover, treatment with PGMI-004A effectively inhibits PGAM1 enzyme activity in tumors in vivo in resected tumors from xenograft nude mice . MCE has not independently confirmed the accuracy of these methods. They are for reference only.
