PGMI-004A |
Catalog No.GC33387
One-Click Copy Product Info
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PGMI-004A is a potent phosphoglycerate mutase 1 (PGAM1) inhibitor with an IC50 of 13.1 μM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1313738-90-7
Sample solution is provided at 25 µL, 10mM.
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PGMI-004A is a potent phosphoglycerate mutase 1 (PGAM1) inhibitor with an IC50 of 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 fluorescence-based binding assay. PGMI-004A may allosterically modulate the enzyme activity of PGAM1. The Ki value is determined to be 3.91±2.50 μM using Dixon plot analysis. The Kd 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[1].
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[1].
[1]. Hitosugi T, et al. Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth. Cancer Cell. 2012 Nov 13;22(5):585-600.
Cell experiment: | For adherent cell viability assay such as H1299 cells with trypan blue exclusion, 5×104 cells are seeded in 6-well plate 24 h before the assay starts and are cultured at 37°C. 24 h after seeding, cells are treated with PGMI-004A (5, 10, 20, and 40 μM) and incubated at 37°C for indicated times. Cell viability is determined by counting drug-treated cells compared to DMSO-treated control cells with trypan blue exclusion under a microscope (×40). For MTT cell viability assay of adherent cells, 5×103 cells are seeded in 96-well plate 24 h before the assay starts and are cultured at 37°C. 24 h after seeding, cells are treated with PGMI-004A and incubated at 37°C for 3 days. Cell viability is determined by using CellTiter96Aqueous One solution proliferation kit[1]. |
Animal experiment: | Mice[1]Nude mice (female 6-8-week-old) are subcutaneously injected with 10×106 H1299 cells harboring empty vector on the left flank, and cells with stable knockdown of endogenous hPGAM1 on the right flank, respectively. The tumors are harvested and weighed at the experimental endpoint, and the masses of tumors (g) derived from cells with and without stable knockdown of endogenous hPGAM1 in both flanks of each mouse are compared. Statistical analyses are performed by comparison in relation to the control group with a two-tailed paired Student’s ttest. For drug evaluation of PGMI-004A using xenograft mice, PGMI-004A is administered by daily i.p. injection at a dose of 100 mg/kg from 6 days after subcutaneous injection of H1299 cells on right flank of each mouse. Tumor growth is recorded by measurement of two perpendicular diameters of the tumors over a 3-week course[1]. |
References: [1]. Hitosugi T, et al. Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth. Cancer Cell. 2012 Nov 13;22(5):585-600. | |
| Cas No. | 1313738-90-7 | SDF | |
| Canonical SMILES | O=S(C(C=C1C2=O)=C(O)C(O)=C1C(C3=C2C=CC=C3)=O)(NC4=CC=C(C(F)(F)F)C=C4)=O | ||
| Formula | C21H12F3NO6S | M.Wt | 463.38 |
| Solubility | DMSO : ≥ 125 mg/mL (269.76 mM);Water : < 0.1 mg/mL (insoluble) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1581 mL | 10.7903 mL | 21.5806 mL |
| 5 mM | 431.6 μL | 2.1581 mL | 4.3161 mL |
| 10 mM | 215.8 μL | 1.079 mL | 2.1581 mL |
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g
μL
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 4 reference(s) in Google Scholar.)