PHGDH-IN-7
PHGDH-IN-7 is an orally active Cys281-targeted covalent noncompetitive PHGDH inhibitor with an enzymatic IC50 of 0.8 μM, MST Kd of 3.4 μM, and Ki of 2.82 μM. PHGDH-IN-7 disrupts PHGDH homodimer formation. PHGDH-IN-7 blocks cellular de novo serine synthesis. PHGDH-IN-7 elevates intracellular ROS levels and inhibits DNA replication. PHGDH-IN-7 resensitizes EGFR-TKI-resistant lung adenocarcinoma cells. PHGDH-IN-7 suppresses triple-negative breast tumor growth with no obvious systemic toxicity. PHGDH-IN-7 serves as a tool compound for PHGDH-dependent tumor research.
For research use only. We do not sell to patients.
- Formula: C32H40N10O2
- Molecular Weight:596.73
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HCC70 | IC50 |
4.8 μM
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Inhibits the growth of HCC70 cells for 72 h.
Inhibits the growth of HCC70 cells for 72 h.
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42284116 |
| MDA-MB-468 | IC50 |
1.8 μM
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Inhibits the growth of MDA-MB-468 cells for 72 h.
Inhibits the growth of MDA-MB-468 cells for 72 h.
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42284116 |
| ZR-75-1 | IC50 |
50.2 μM
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Inhibits the growth of ZR-75-1 cells for 72 h.
Inhibits the growth of ZR-75-1 cells for 72 h.
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42284116 |
| PC-9 | IC50 |
2.3 μM
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Inhibits the growth of PC-9 cells for 72 h.
Inhibits the growth of PC-9 cells for 72 h.
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42284116 |
| HCT-116 | IC50 |
5.3 μM
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Inhibits the growth of HCT-116 cells for 72 h.
Inhibits the growth of HCT-116 cells for 72 h.
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42284116 |
PHGDH-IN-7 (Compound D5-2) (72 h) exhibits potent activity against PHGDH-dependent MDA-MB-468 cells with a cellular IC50 of 1.8 μM, and displays markedly weaker anti-proliferative effects in PHGDH-independent cell lines[1].
PHGDH-IN-7 (40 μM; 3 min) effectively targets PHGDH protein in MDA-MB-468 cells[1].
PHGDH-IN-7 (1.5-3 μM; 48 h) relies primarily on PHGDH for its antiproliferative potency in MDA-MB-468 cells[1].
PHGDH-IN-7 (2.5-10 μM; 8 h) inhibits the serine synthesis in MDA-MB-468 cells[1].
PHGDH-IN-7 (2.5-10 μM; 24 h) suppresses DNA synthesis and elevates intracellular ROS levels in MDA-MB-468 cells[1].
PHGDH-IN-7 (1-5 μM; 48 h) impairs clonogenic growth of MDA-MB-468 and HCT116 cells[1].
PHGDH-IN-7 (5-20 μM; 2 weeks) preferentially inhibits colony formation of PHGDH-high HCC827ER9 cells compared to PHGDH-low parental HCC827 and HCC827OR lines[1].
PHGDH-IN-7 (1-2 μM; 48 h) restores Erlotinib (HY-50896) sensitivity to HCC827ER9 cells and produces synergistic antiproliferative effects[1].
PHGDH-IN-7 (5-10 μM; 48 h) requires higher concentrations to resensitize Osimertinib (HY-15772)-resistant HCC827OR cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MDA-MB-468 cells
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Concentration:40 μM
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Incubation Time:3 min
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Result:Decreased the thermal stability of PHGDH in MDA-MB-468 cells.
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Cell Line:MDA-MB-468 cells
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Concentration:1.5 μM, 3 μM
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Incubation Time:48 h
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Result:Displayed markedly weakened inhibitory activity against MDA-MB-468 cells following PHGDH RNAi knockdown.
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Cell Line:MDA-MB-468 cells
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Concentration:2.5 μM, 5 μM, 10 μM
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Incubation Time:24 h
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Result:Suppressed DNA synthesis in MDA-MB-468 cells, as measured by EdU incorporation.
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Cell Line:MDA-MB-468 cells, HCT116 cells
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Concentration:1 μM, 2.5 μM, 5 μM
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Incubation Time:48 h
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Result:Reduced the clonogenic capacity of MDA-MB-468 and HCT116 cells.
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Cell Line:HCC827ER9 cells, HCC827 cells, HCC827OR cells
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Concentration:5 μM, 10 μM, 20 μM
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Incubation Time:2 weeks
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Result:Exhibited potent inhibition against PHGDH-high HCC827ER9 cells.
Showed weaker activity against PHGDH-low parental HCC827 and HCC827OR cells.
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Cell Line:HCC827ER9 cells
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Concentration:1 μM, 2 μM
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Incubation Time:48 h
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Result:Significantly restored Erlotinib (HY-50896) sensitivity in HCC827ER9.
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Cell Line:HCC827OR cells
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Concentration:5 μM, 10 μM
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Incubation Time:48 h
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Result:Needed higher concentrations to resensitize HCC827OR cells to Osimertinib (HY-15772).
| Species | Dose | Route | Cmax | Tmax | T1/2 | AUC0-t | CL | Vss | MRT0-t | F |
|---|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 10 mg/kg | i.v. | 50390 ng/mL | 0.083 h | 0.16 h | 100763 ng/mL·h | 1.68 mL/min/kg | 24 mL/kg | 0.0033 h | / |
| Mice[1] | 30 mg/kg | i.p. | 15601 ng/mL | 0.33 h | 0.74 h | 22697 ng/mL·h | / | / | 1.14 h | 7.51 % |
| Mice[1] | 30 mg/kg | p.o. | 16929 ng/mL | 0.33 h | 0.20 h | 8545 ng/mL·h | / | / | 0.38 h | 2.83 % |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female NOD-SCID mice bearing MDA-MB-468 triple-negative breast cancer xenografts[1]
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Dosage:25 mg/kg, 50 mg/kg
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Administration:i.p.; twice daily; for 21 days
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Result:Did not cause noticeable loss in body weight, and no other signs of toxicity were observed at two dosages.
Significantly inhibited tumor size and weight.
Chemical Information
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Molecular Weight 596.73
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Formula C32H40N10O2
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SMILES
CNC1=NC(N[C@H](C(N)=O)CC2=CC=C(C3=CC=C(N(C)C)N=C3)C=C2)=NC(N4CC[C@]5(CCN(C(C#CC)=O)C5)CC4)=N1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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