Vadadustat prodrug-1
Vadadustat prodrug-1 is a near-infrared activated photocaged, blood-brain barrier-permeable neuroprotective prodrug of Vadadustat (HY-101277). Vadadustat prodrug-1 masks the acidic pharmacophore of Vadadustat, and releases active Vadadustat upon irradiation at 650 nm to inhibit PHD2. Vadadustat prodrug-1 reduces cell damage, infarct volume and cerebral edema, and promotes neurological function recovery. Vadadustat prodrug-1 can be used for the research of ischemic stroke.
For research use only. We do not sell to patients.
- Formula: C44H40BClN4O6
- Molecular Weight:767.08
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Vadadustat prodrug-1 (Compound 11) (100 μM; 1-10 min irradiation) enables complete and rapid near-infrared-induced photorelease of Vadadustat (HY-101277) within 10 min under physiological conditions, and exhibits excellent stability under white light, reductive environments and physiological temperatures[1].
Vadadustat prodrug-1 (10 min irradiation prior to 1 h incubation) potently inhibits PHD2 only after 10 min of irradiation at 650 nm, with an IC50 of 71.6 nM, and shows no activity under dark conditions[1].
Vadadustat prodrug-1 (5-10 μM; 24 h reoxygenation, 10 min irradiation where applicable) exerts dose-dependent neuroprotective effects on HT22 cells treated with oxygen-glucose deprivation/reoxygenation (OGD/R). It enhances cell viability, increases the number of viable cells and reduces the number of dead cells only after 10 min of 650 nm irradiation, with no effect under dark conditions[1].
Vadadustat prodrug-1 (5-10 μM; 10 min irradiation where applicable) dose-dependently stabilizes HIF-1α in HT22 cells, reduces OGD/R-induced ROS accumulation, restores SOD activity and mitochondrial membrane potential, and decreases MDA levels [1], but only after 10 min of irradiation with 650 nm light.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HT22 cells (oxygen-glucose deprivation/reoxygenation (OGD/R) treated)
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Concentration:5, 10 μM
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Incubation Time:24 h (reoxygenation; 10 min irradiation where applicable)
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Result:Improved cell viability in a dose-dependent manner with 650 nm irradiation, with efficacy comparable to Vadadustat.
Showed no protective effect without irradiation, with cell viability matching the OGD/R control group.
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Cell Line:HT22 cells
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Concentration:5-10 μM
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Incubation Time:10 min (irradiation where applicable)
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Result:Dose-dependently upregulated HIF-1α protein levels in HT22 cells after 10 min of 650 nm irradiation, with an effect comparable to equimolar concentrations of Vadadustat.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:ICR mice[1]
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Dosage:20 mg/kg; 50 mg/kg
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Administration:s.c.; 30 minutes pre-surgery, repeated at 24 and 48 hours post-surgery; each dose followed by 650 nm light irradiation for 10 min
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Result:Reduced cerebral infarct area by 33% at 20 mg/kg, comparably to positive control edaravone.
Decreased brain water content at 20 mg/kg, outperforming edaravone.
Improved modified neurological severity score (mNSS) more effectively than edaravone at 20 mg/kg.
Reduced cerebral infarct area by 53% at 50 mg/kg.
Decreased brain water content at 50 mg/kg.
Provided superior dose-dependent improvement in mNSS at 50 mg/kg compared to 20 mg/kg dose and edaravone.
Upregulated HIF-1α levels in brain tissue in a dose-dependent manner at both doses.
Partially restored hippocampal architecture at both doses, with 50 mg/kg dose significantly increasing thickness and regularity of pyramidal layers in CA1 and CA3 regions.
Improved postoperative survival outcomes in a dose-dependent manner at both doses.
Chemical Information
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Molecular Weight 767.08
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Formula C44H40BClN4O6
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SMILES
ClC1=CC(C2=CN=C(C(O)=C2)C(NCC(OCC(C3=CC4=C(N3[B-](C)5C)C(C=CC(OC)=C6)=C6CC4)=C7[N+]5=C8C9=C(CCC8=C7)C=C(OC)C=C9)=O)=O)=CC=C1
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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)