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| Targets |
PGAM1 (phosphoglycerate mutase 1). PGMI-004A is a potent and selective PGAM1 inhibitor with an IC50 of approximately 13.1 μM and a Ki of 3.91 μM. The Kd value of the PGMI-004A-PGAM1 interaction is 7.2 ± 0.7 μM.
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| ln Vitro |
PGMI-004A inhibits PGAM1 with an IC50 of about 13.1 μM, and the PGMI-004A-PGAM1 response's fluorescence-determined Kd value is 7.2 μM. To control PGAM1 activity, PGMI-004A can alter the structure of the enzyme. The protein-ligand complex's Kd value was computed to be 9.4 μM, and the Ki value was found to be 3.91 μM using Dixon plot analysis. PGMI-004A (20 μM) treatment inhibiting PGAM1 activity led to lower 2-PG and higher 3-PG levels in H1299 cells, which could be restored by methyl-2-PG treatment. Lactate production was significantly reduced after treatment with PGMI-004A (20 μM), and intracellular ATP levels were not significantly affected by treatment with methyl 2-PG, but lactate production was restored. Treatment with PGMI-004A (20 μM) decreased the amount of oxidized PPP and NADPH/NADP+ amplification, caused anemia, decreased RNA biosynthesis, and decreased H1299 cell proliferation. Human cancer and leukemia cells treated with PGMI-004A showed decreased cell proliferation, while human dermal fibroblasts (HDF), human foreskin fibroblasts (HFF), human cells pretreated with HaCaT, and human melanopiginated PIG1 cells did not show this effect. PGMI-004A's minimally non-toxic effects on normally proliferating human cells are indicated [1].
PGMI-004A inhibits PGAM1 with an IC50 of approximately 13.1 μM and a Ki of 3.91 μM. The Kd value of the PGMI-004A-PGAM1 interaction is 7.2 ± 0.7 μM. PGMI-004A treatment significantly inhibits the proliferation of various human cancer and leukemia cells but has no significant effect on normal human cells. |
| ln Vivo |
In xenograft research, mice that were not clothed were given injections of H1299 cells. Volunteers (n = 8/group) received PGMI-004A (100 mg/kg/day) or vehicle for 21 days following injection, starting six days after the injection. When PGMI-004A was administered to treated mice, compared to vehicle-control mice, there were notable decreases in tumor growth and size. Furthermore, xenografted nude mouse tumors' PGAM1 enzyme activity can be successfully inhibited by PGMI-004A therapy [1].
PGMI-004A inhibits cancer cell proliferation by blocking PGAM1 activity. Inhibition of PGAM1 by PGMI-004A results in increased 3-PG and decreased 2-PG levels in cancer cells, leading to significantly decreased glycolysis, PPP flux, and biosynthesis, as well as attenuated cell proliferation and tumor growth. It is a promising compound for cancer therapy. |
| Enzyme Assay |
PGAM1 enzyme activity assays are performed using recombinant human PGAM1 enzyme. The enzyme is incubated with the substrate 3-phosphoglycerate (3-PG) in assay buffer (50 mM Tris-HCl pH 7.4, 1 mM EDTA, 1 mM DTT). The reaction product 2-phosphoglycerate (2-PG) is quantified by a coupled enzyme assay or by HPLC. PGMI-004A is serially diluted and added to the reaction mixture. IC50 and Ki values are determined by non-linear regression analysis. Each concentration is tested in duplicate. Binding affinity (Kd) is determined by fluorescence-based binding assays.
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| Cell Assay |
Cellular PGAM1 inhibition is evaluated in cancer cell lines. Cells are cultured in appropriate media at 37°C with 5% CO2 and treated with PGMI-004A at various concentrations for 24-72 hours. 2-PG and 3-PG levels in cell lysates are measured by LC-MS/MS. Glycolysis flux is assessed by measuring lactate production and glucose consumption. Cell viability and proliferation are assessed using MTT or CellTiter-Glo assays. Each experiment includes vehicle controls.
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| Animal Protocol |
In vivo efficacy is evaluated in mouse xenograft models using cancer cell lines. PGMI-004A is administered orally or intraperitoneally at doses determined by preclinical studies. Tumor growth is monitored by caliper measurements. At study endpoint, tumors are harvested for histopathological analysis and biochemical assays (2-PG/3-PG levels, glycolysis markers). Body weight and clinical signs are monitored throughout the study. Sample sizes typically range from 6-10 animals per group.
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| ADME/Pharmacokinetics |
Molecular Weight: 478.40. Formula: C21H13F3N2O6S. CAS No.: 1313738-90-7. Target: PGAM1. IC50: 13.1 μM. For research use only.
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| Toxicity/Toxicokinetics |
No comprehensive toxicology data are publicly available. As a PGAM1 inhibitor targeting glycolysis, potential toxicities may include effects on normal cells that rely on glycolysis for energy. However, PGMI-004A shows no significant effect on normal human cells. Standard toxicity studies would include acute and subchronic toxicity in rodents, genotoxicity screening, and evaluation of effects on metabolism. No clinical trials have been reported for this compound. The compound is intended for research use only.
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| References | |
| Additional Infomation |
PGMI-004A is a specific small molecule inhibitor of phosphoglycerate mutase 1 (PGAM1) with an IC50 of 13.1 μM and a Ki of 3.91 μM. It is a promising compound for cancer therapy due to its ability to inhibit PGAM1, thereby disrupting cancer cell metabolism and proliferation. No clinical trials or regulatory approvals have been reported. The compound is for research use only.
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| Molecular Formula |
C21H12F3NO6S
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| Molecular Weight |
463.3832
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| Exact Mass |
463.034
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| CAS # |
1313738-90-7
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| PubChem CID |
66521681
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.846
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
32
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| Complexity |
849
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
XKVNBCMGEUDKNP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H12F3NO6S/c22-21(23,24)10-5-7-11(8-6-10)25-32(30,31)15-9-14-16(20(29)19(15)28)18(27)13-4-2-1-3-12(13)17(14)26/h1-9,25,28-29H
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| Chemical Name |
3,4-dihydroxy-9,10-dioxo-N-[4-(trifluoromethyl)phenyl]anthracene-2-sulfonamide
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| Synonyms |
PGMI 004A; PGMI004A; PGMI-004A
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 50 mg/mL (~107.90 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.49 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.49 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1581 mL | 10.7903 mL | 21.5806 mL | |
| 5 mM | 0.4316 mL | 2.1581 mL | 4.3161 mL | |
| 10 mM | 0.2158 mL | 1.0790 mL | 2.1581 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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