APH02174
Based on 1 Customer Validation
APH02174 is an orally effective and selective IRAK4 PROTAC degrader with a DC50 of 4.01 nM in THP-1 cells. APH02174 inhibits LPS (HY-D1056)-induced IL-6 release by degrading IRAK4 and blocking TLR/IL-1R downstream signaling. APH02174 exhibits favorable anti-inflammatory activity in both Imiquimod (HY-B0180)-induced psoriasis-like skin inflammation and collagen-induced arthritis models. APH02174 is useful for research on inflammatory diseases such as psoriasis and rheumatoid arthritis.
(Pink: IRAK4 ligand (HY-174470); Blue: Cereblon ligand (HY-45512); Black: linker).
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 純度 : 99.19%
- CAS 番号: 3065494-66-5
- 分子式: C49H55N7O8
- 分子量:870.00
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保管条件:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
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溶剤 & 溶解度
- プロトコル
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
PROTACs アイソフォーム固有の製品をすべて表示
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生物活性
製品説明
IC50 & Target
[1]|
IRAK4 |
Cereblon |
IL-6 |
体外実験
APH02174 (24 h) effectively degrades IRAK4 in THP-1-HiBiT-IRAK4 cells with a DC50 of 4.01 nM and a Dmax of 94%[1].
APH02174 (0.05-1000 nM; 24 h) effectively degrades IRAK4 in human PBMCs with a DC50 of 0.43 nM and a Dmax of 94%[1].
APH02174 (0.03-2000 nM; 24 h) inhibits LPS (HY-D1056)-induced IL-6 release in human PBMCs with an IC50 of 16.43 nM[1].
APH02174 (300 nM; 24 h) selectively degrades IRAK4 in human PBMCs[1].
APH02174 (1 μM) does not degrade SALL4, IKZF1, or IKZF3 in human PBMCs at a concentration of 1 μM[1].
APH02174 (5 μM; 120 min) exhibits relatively low permeability in Caco-2 cells, with a Papp (A→B) of 0.09 × 10−6 cm/s and an efflux ratio of 2.22[1].
APH02174 (10 μM; 5-30 min) shows low inhibitory effects on CYP isozymes in human liver microsomes[1].
APH02174 (3 μM; 5 min) exhibits moderate hERG inhibition with an inhibition rate of 53%[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human PBMCs
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Concentration:0.24, 0.98, 3.91, 15.63, 62.50, 250.00 and 1000.00 nM
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Incubation Time:24 h
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Result:Degraded IRAK4 in human PBMCs in a concentration-dependent manner, with a DC50 of 0.43 nM and a Dmax of 94%.
Parmacokinetics
| Species | Dose | Route | Cmax | AUClast | T1/2 | CL | Vss | Tmax | F |
|---|---|---|---|---|---|---|---|---|---|
| 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 % |
| 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 % |
体内実験
APH02174 (10-100 mg/kg; p.o.; twice daily; 6 days) dose-dependently attenuates IMQ-induced psoriasis-like skin inflammation in mice[1].
APH02174 (30-100 mg/kg; p.o.; twice daily; 14 days) effectively alleviates arthritis symptoms in the CIA mouse model by degrading IRAK4 in PBMCs[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Cynomolgus monkeys (4 years old)[1]
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Dosage:20 mg/kg
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Administration:p.o.; single dose
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Result:Degraded 83% of IRAK4 in cynomolgus monkey PBMCs at 48 h postadministration.
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Animal Model:C57BL/6 mice (7-week-old)[1]
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Dosage:10, 30, 100 mg/kg
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Administration:p.o.; twice daily; from day 0 to day 6
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Result:Showed a dose-dependent reduction in erythema intensity and scaling, with near-complete resolution of crusts and restoration of normal skin texture at 100 mg/kg.
Decreased delta ear thickness significantly in the 10, 30, and 100 mg/kg groups.
Exhibited a significant reduction in spleen weight in the 30 and 100 mg/kg groups.
Induced dose-dependent IRAK4 degradation in splenic tissue, with 30 and 100 mg/kg achieving >80% depletion, and the 10 mg/kg dose inducing 75% degradation.
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Animal Model:DBA/1 mice (male)[1]
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Dosage:30, 100 mg/kg
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Administration:p.o.; twice daily; for 14 days
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Result:Significantly attenuated clinical scores at 30 and 100 mg/kg.
Significantly improved delta paw volume and histopathological scores at 30 and 100 mg/kg.
Markedly degraded IRAK4 in mouse PBMCs at 30 and 100 mg/kg.
化学情報
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CAS 番号 3065494-66-5
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性状 Solid
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分子量 870.00
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分子式 C49H55N7O8
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Color White to off-white
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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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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
溶剤 & 溶解度
体外:
DMSO : 50 mg/mL (57.47 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
純度とドキュメンテーション
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データシート (278 KB)
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SDS (252 KB)
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取扱説明書 (2659 KB)
参考文献
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.1494 mL | 5.7471 mL | 11.4943 mL | 28.7356 mL |
| 5 mM | 0.2299 mL | 1.1494 mL | 2.2989 mL | 5.7471 mL | |
| 10 mM | 0.1149 mL | 0.5747 mL | 1.1494 mL | 2.8736 mL | |
| 15 mM | 0.0766 mL | 0.3831 mL | 0.7663 mL | 1.9157 mL | |
| 20 mM | 0.0575 mL | 0.2874 mL | 0.5747 mL | 1.4368 mL | |
| 25 mM | 0.0460 mL | 0.2299 mL | 0.4598 mL | 1.1494 mL | |
| 30 mM | 0.0383 mL | 0.1916 mL | 0.3831 mL | 0.9579 mL | |
| 40 mM | 0.0287 mL | 0.1437 mL | 0.2874 mL | 0.7184 mL | |
| 50 mM | 0.0230 mL | 0.1149 mL | 0.2299 mL | 0.5747 mL |
APH02174 関連分類
HY-174455 関連分類
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