DC-PGKI
DC-PGKI is an orally active ATP-competitive PGK1 inhibitor(IC50 = 0.16 Μm, Kd = 99.08 nM). DC-PGKI stabilizes PGK1 in vitro and in vivo, and suppresses both glycolytic activity and the kinase function of PGK1. DC-PGKI-mediated inhibition of PGK1 leads to the accumulation of NRF2 (nuclear factor-erythroid factor 2-related factor 2, NFE2L2), which then translocates to the nucleus, binds to the proximal regions of IL-1β and IL-6 genes, and suppresses the LPS-induced expression of these genes. DC-PGKI can be used for the study of colitis.
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- No. CAS: 2829198-49-2
- Fòrmula: C26H29Cl2N7O3
- Peso molecular:558.46
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Actividad biológica
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PGK1 0.16 μM (IC50) |
PGK1 99.08 nM (Kd) |
IL-6 |
IL-1β |
DC-PGKI (0.1-30 μM, 3 h) can increase RAW264.7 cells' PGK1 thermal stability in a concentration-dependent manner[1].
DC-PGKI (5-10 μM, 10 h) inhibits PGK1 glycolytic metabolic activity in the resting and activated in RAW264.7 cells[1].
DC-PGKI (10-20 μM) notably decreases the Ser30 phosphorylation level of Beclin1 in RAW246.7 cells, indicating that DC-PGKI also impairs PGK1’s kinase function[1].
DC-PGKI (5-20 μM) inhibits LPS-induced IL-1β and IL-6 mRNA in a concentration-dependent manner in RAW246.7 cells[1].
DC-PGKI (0-20 μM) significantly inhibits Lipopolysaccharides (HY-D1056) (LPS)-induced precursor of IL-1β and IL-6 in RAW264.7 cells[1].
DC-PGKI (5-20 μM, 7 h) results in a significant reduction in KEAP1 protein level, accumulation of NRF2, as well as upregulation of both the mRNA and protein levels of HMOX1 in LPS-induced RAW264.7 cells[1].
DC-PGKI (5-20 μM, 7 h) upregulates other downstream target genes of NRF2, including Txnrd1, Prdx1, Gclc, Sod1, Fth1, and Ephx1, in both LPS-treated and untreated conditions in RAW264.7 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:RAW264.7 cells
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Concentration:0 μM, 0.1 μM, 0.5 μM, 1 μM, 5 μM, 10 μM, 20 μM, 30 μM
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Incubation Time:3 h
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Result:Increased RAW264.7 cells' PGK1 thermal stability in a concentration-dependent manner.
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Cell Line:RAW264.7 cells were stimulated with LPS (1 μg/mL) for 4 hours.
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Concentration:5 μM, 10 μM, 20 μM
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Incubation Time:7 h
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Result:Inhibited the mRNA expression of IL-1β and IL-6.
Resulted in a significant reduction in KEAP1 protein level, accumulation of NRF2, as well as upregulation of both the mRNA and protein levels of HMOX1.
Upregulated other downstream target genes of NRF2, including Txnrd1, Prdx1, Gclc, Sod1, Fth1, and Ephx1.
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUClast | MRTINF_obs | F | AUCINF_obs | Vss_obs |
|---|---|---|---|---|---|---|---|---|---|---|
| Mice | 10 mg/kg | p.o. | 5.29 h | 4 h | 38 ng/mL | 253 ng·h/mL | 8.1 h | 11.2 % | / | / |
| Mice | 3 mg/kg | i.v. | 4.35 h | / | / | 676 ng·h/mL | 5.36 h | / | 755 ng·h/mL | 22362 mL/kg |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:8-week-old C57BL/6 male mice were given 5%(w/v) DSS for 7 days to induce acute colitis, followed by drinking water for one day[1].
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Dosage:5 mg/kg, 10 mg/kg
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Administration:P.o., once daily for 8 days
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Result:Significantly reduced weight loss induced by DSS.
The disease activity index (DAI) decreased compared to the DSS group.
Reduced colonic tissue damage, lymphocyte infiltration, and crypt destruction.
Lowered serum and tissue protein and mRNA levels of IL-1β and IL-6.
Increased NRF2 protein accumulation in colonic tissue.
Chemical Information
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No. CAS 2829198-49-2
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Peso molecular 558.46
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Fòrmula C26H29Cl2N7O3
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SMILES
O=C(N1CCN(C2=NC3=C(N=C2C(OCC)=O)C=C(Cl)C(Cl)=C3)CC1)NC(C=C4)=CC=C4N5CCNCC5
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
DC-PGKI Related Classifications
HY-177944 Related Classifications
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