TP0463518

SKU: orb1301829

Description

TP-0463518 is a potent small molecule inhibitor of HIF prolyl hydroxylase (PHD), demonstrating high activity with IC50 values of 13 nM for human PHD2 and 18 nM for rat PHD2. This compound is a valuable research tool for studying hypoxia signaling pathways and has been utilized in both cellular and animal models to investigate conditions like anemia and ischemia.

Research Area

Epigenetics & Chromatin, Metabolism Research

Key Properties

• CAS Number: 1558021-37-6
• MW: 431.83
• Purity: 99.52% (May vary between batches)
• Formula: C₂₀H₁₈ClN₃O₆
• SMILES: OC(=O)CNC(=O)C1=C(O)CCN(Cc2ccc(Oc3ccc(Cl)cc3)nc2)C1=O
• Target: HIF/HIF Prolyl-Hydroxylase
• Solubility: DMSO:110 mg/mL (254.73 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (9.26 mM)

Bioactivity

• Target IC50:
  PHD3 (human):63 nM (cell free)|PHD2 (human):13 nM (cell free)|PHD2 (rat):18 nM (cell free)|PHD1 (human):18 nM (cell free)
• In Vivo:
  In normal mice and rats, TP0463518 significantly increased the serum EPO levels at doses of 5 and 20 mg/kg, respectively. TP0463518 also increased the serum EPO level in 5/6 nephrectomized chronic kidney disease model rats at a dose of 10 mg/kg, with a correlation factor for serum EPO and the serum TP0463518 levels of 0.82. TP0463518 was promptly removed with a half-life of 5.2 h and increased the area under the curve (AUC) of EPO at a dose of 5 mg/kg.
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• In Vitro:
  TP0463518 competitively inhibited human PHD2 with a Ki value of 5.3 nM. TP0463518 also inhibited human PHD1/3 with IC50 values of 18 and 63 nM as well as monkey PHD2 with an IC50 value of 22 nM.
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• Animal Research:
  Nine-week-old Balb/c mice were randomly assigned to a vehicle or a 5 to 40 mg/kg dose of TP0463518 group. The mice were orally treated with 0.5% methylcellulose or a TP0463518 dosing suspension. Blood was collected at 6 h after administration from the orbital plexus under deep anesthesia, and euthanasia was performed without awakening. An aliquot of blood was mixed with EDTA, and the remaining blood sample was left to stand at room temperature for 15 min. The samples were then centrifuged (2130 x g for 10 min at 4°C) to prepare the plasma and serum.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

TP-0463518, TP0463518, TP 0463518, PHD3, PHD1, PHD2, inhibit, Inhibitor, HIF/HIF ProlylHydroxylase, HIF Prolyl-Hydroxylase, HIF ProlylHydroxylase, HIF, HIFs, HIFProlylHydroxylase, HIF-PH, HIF/HIF Prolyl-Hydroxylase, HIF/HIFProlylHydroxylase, Hypoxia-inducible factors

Compound Identifiers

PubChem CID

73052863