PD-305
PD-305 is a selective PTPN2 PROTAC degrader, with DC50 values of 0.25 nM and 5.11 nM against PTPN2 and PTPN1, respectively. PD-305 enhances IFN-γ-induced STAT1 phosphorylation, inhibits the proliferation of IFN-γ-stimulated colorectal cancer cells, promotes CD8+ T cell activation, enhances the tumor-killing activity of T cells, and suppresses tumor growth in mouse models. PD-305 can be used for the research of colorectal cancer.
(Pink: PTPN2 ligand (HY-184259); Blue: Cereblon ligand (HY-184258); Black: linker).
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- Formule: C43H42F4N6O10S
- Masse moléculaire:910.89
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
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PTPN2 0.25 nM (DC50) |
PTPN1 5.11 nM (DC50) |
Cereblon |
STAT1 |
STAT5 |
PD-305 (0.001-10000 nM; up to 24 h) induces time- and concentration-dependent PTPN2 degradation in transfected HEK293T cells, and causes prolonged PTPN2 downregulation that persists for 24 h after compound removal[1].
PD-305 (1-10000 nM; 24 h) enhances IFN-γ-induced STAT1 phosphorylation in HT-29 human colorectal cancer cells at nanomolar concentrations via PTPN2 degradation[1].
PD-305 (various concentrations; 72 h) potently inhibits the proliferation of IFN-γ-stimulated HT-29 human colorectal cancer cells with an IC50 of 11.95 nM, nearly 80-fold more potent than AC484[1].
PD-305 (0.2-20 μM; 0-24 h) enhances T-cell receptor signaling via increased LCK phosphorylation and promotes cytokine-induced STAT5 phosphorylation in Jurkat cells through PTPN2 degradation[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Jurkat cell line
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Concentration:1 μM (pretreatment for α-CD3 stimulation); 0.2, 2 and 20 μM (incubation with IFN-γ or IL-2)
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Incubation Time:24 h (pretreatment; incubation with IFN-γ or IL-2); 0-20 min (α-CD3 stimulation)
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Result:Upregulated α-CD3-stimulated LCK phosphorylation in Jurkat cells.
Promoted IFN-γ- and IL-2-induced STAT5 phosphorylation, which correlated with reduced PTPN2 protein levels.
PD-305 (10-25 mg/kg; i.p.; every other day; 20 days) significantly reduces MC38 tumor volume and weight in C57BL/6 mice without affecting body weight[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (female, 6-8 weeks old, 18-22 g, subcutaneously injected with 1 × 105 MC38 cells)[1]
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Dosage:50 mg/kg
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Administration:i.v.; single dose
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Result:Induced almost complete PTPN2 degradation in tumor tissues, with remaining PTPN2 levels near 0% of vehicle control.
Induced modest degradation of PTPN1, with remaining PTPN1 levels ~60% of vehicle control.
Increased the proportion of CD69-positive CD8+ T cells in vivo to ~35% at 24 hours post-injection.
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Animal Model:C57BL/6 (female, 6-8 weeks old, 18-22 g, subcutaneously injected with 1 × 105 MC38 cells)[1]
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Dosage:10 mg/kg; 25 mg/kg
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Administration:i.p.; every other day; 20 days
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Result:Significantly suppressed MC38 tumor growth compared to vehicle control.
Reduced mean tumor weight to ~1.3 g (10 mg/kg) and ~1.1 g (25 mg/kg) at day 21, compared to ~2.0 g in vehicle-treated mice.
Caused no significant changes in body weight relative to vehicle.
Chemical Information
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Masse moléculaire 910.89
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Formule C43H42F4N6O10S
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SMILES
O=C(N1CCC(C#CC2=C(C)C=C(O)C(N3CC(NS3(=O)=O)=O)=C2F)C1)C(C4)CC4N(CC5)CCC5C6=C(C=CC=C7C8=O)C7=C(N8C9CCC(NC9=O)=O)C=C6.O=C(O)C(F)(F)F
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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