| Description | Zimlovisertib (PF-06650833) is an effective, selective and orally active inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4) (IC50s: 0.2 and 2.4 nM in the cell and PBMC assay). |
| In vitro | PF06650833（化合物40）的激酶选择性剖析是通过在200 nM抑制剂浓度下，使用每种激酶的ATP Km值，在278种激酶的组合中进行评估的。IRAK4观察到约100%的抑制效果。对于全细胞功能性VEGF2R评估（PAE-KDR细胞系），内酰胺PF06650833显示出在高达30 μM的浓度下无活性。在电压钳制实验中，PF06650833在100 μM时能抑制hERG电流25%。 |
| In vivo | PF06650833 (0.3-30 mg/kg；口服；给药后2.5小时；雄性SD大鼠) 处理显著以剂量依赖性抑制LPS诱导的TNF-α。经口给予PF06650833后2.5小时，PF06650833在血浆中的平均暴露量分别为2.1 nM、7.7 nM、19 nM和150 nM自由状态，对应的给药剂量分别为0.3、1、3和30 mg/kg。PF06650833在大鼠血浆中的非结合部分比例为0.3。 |
| Animal experiments | Animal Model: Male Sprague-Dawley rats. Dosage: 0.1 mg/kg, 1 mg/kg, 3 mg/kg, 30 mg/kg. Administration: Oral administration; for 2.5 hours |
| Target activity | IRAK4:0.2 nM |
| Synonyms | PF-06650833, PF06650833 |
| molecular weight | 361.37 |
| Molecular formula | C18H20FN3O4 |
| CAS | 1817626-54-2 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 100 mg/mL (276.72 mM) |
| References | 1. Lee KL, et al. Discovery of Clinical Candidate 1-{[(2S,3S,4S)-3-Ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-7-methoxyisoquinoline-6-carboxamide (PF-06650833), a Potent, Selective Inhibitor of Interleukin-1 Receptor Associated Kinase 4 (IRAK4), by Fragment-Based Drug Design. J Med Chem. 2017 Jul 13;60(13):5521-5542. |