APH02174
APH02174 is a highly selective and orally active IRAK4 PROTAC degrader with the DC50 of 4.01 nM in THP-1 cells. APH02174 blocks inflammatory signals by inhibiting IL-6 release. APH02174 can be used for research on inflammatory conditions such as psoriasis vulgaris and rheumatoid arthritis.
(Pink: IRAK4 ligand (HY-174470); Blue: Cereblon ligand (HY-45512); Black: linker).
For research use only. We do not sell to patients.
- CAS No.: 3065494-66-5
- Formula: C49H55N7O8
- Molecular Weight:870.00
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
|
Cereblon |
IRAK4 4.01 nM (DC50) |
IL-6 |
APH02174 (0.24-1000 nM) can selectively degrade IRAK4 protein in various cells, including THP-1 (DC50 = 4.01 nM), hPBMCs (DC50 = 0.43 nM) and mouse PBMCs (DC50 = 3.57 nM) [1].
APH02174 (0.03-2000 nM; 24 h) significantly inhibits the Lipopolysaccharides (LPS) (HY-D1056) induced IL-6 release in the hPBMCs (IC50 = 16.43 nM) [1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | Cmax | AUClast | T1/2 | CL | Vss | Tmax | F |
|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 10 mg/kg | p.o. | 2073 ng/mL | 23388 ng·h/mL | 4.34 h | / | / | 2.67 h | 45 % |
| Mice[1] | 2 mg/kg | i.v. | 1867 ng/mL | 10556 ng·h/mL | 3.78 h | 3.13 mL/min/kg | 0.880 L/kg | / | / |
| Rat[1] | 2 mg/kg | i.v. | 1420 ng/mL | 2589 ng·h/mL | 4.00 h | 12.8 mL/min/kg | 2.66 L/kg | / | / |
| Rat[1] | 30 mg/kg | p.o. | 613 ng/mL | 7093 ng·h/mL | 3.43 h | / | / | 6.00 h | 18 % |
| Cynomolgus Monkey[1] | 1 mg/kg | i.v. | 672 ng/mL | 1818 ng·h/mL | 8.67 h | 9.20 mL/min/kg | 3.85 L/kg | / | / |
| Cynomolgus Monkey[1] | 20 mg/kg | p.o. | 229 ng/mL | 3997 ng·h/mL | 9.07 h | / | / | 6.00 h | 11 % |
| Dog[1] | 1 mg/kg | i.v. | 599 ng/mL | 3669 ng·h/mL | 8.10 h | 4.75 mL/min/kg | 2.73 L/kg | / | / |
| Dog[1] | 5 mg/kg | p.o. | 360 ng/mL | 6994 ng·h/mL | 10.6 h | / | / | 4.00 h | 39 % |
APH02174 (30-100 mg/kg; p.o.; once daily; for 14 days) significantly improves arthritis in the rheumatoid arthritis mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Collagen-induced psoriasis male DBA/1 mice (7 weeks)[1]
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Dosage:30 or 100 mg/kg
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Administration:Oral administration (p.o.); once daily for 14 days
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Result:Significantly improved arthritis score and reduced inflammation.
Significantly reduced pathological scores and improved pathological structural changes.
Significantly degraded IRAK4 in mouse PBMCs.
Chemical Information
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CAS No. 3065494-66-5
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Appearance Solid
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Molecular Weight 870.00
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Formula C49H55N7O8
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SMILES
OCC1CCN(CC1)C2=CC3=C(C=C2NC(C4=COC5=C4N=CC=C5)=O)CC6(CCN(CC6)C[C@@H]7CC[C@@H](OCC#CC8=C(C(N(C9=O)C%10C(NC(CC%10)=O)=O)=CC=C8)N9C)CC7)O3
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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