Zimlovisertib (PF-06650833) 是一种有效的，选择性的和口服可生物利用的白介素-1 受体相关激酶 4 (IRAK4) 的抑制剂，其 IC₅₀ 值为 0.2 nM，在 PBMC 分析中，IC₅₀ 值为 2.4 nM。Zimlovisertib 有潜力用于类风湿性关节炎，狼疮和淋巴瘤等疾病的研究。

Zimlovisertib (PF-06650833) is a potent, selective and orally active inhibitor of interleukin-1 receptor associated kinase 4 (IRAK4) with IC 50 s of 0.2 and 2.4 nM in the cell and PBMC assay, respectively. Zimlovisertib is used to treat diseases such as rheumatoid arthritis, lupus, and lymphomas.

Solid

IRAK4 0.2 nM (IC50)

The kinome selectivity profile of Zimlovisertib (Compound 40) is assessed in a panel of 278 kinases (Invitrogen) at 200 nM inhibitor concentration using the ATP Km for each kinase. Approximately 100% inhibition is observed for IRAK4.
Lactam Zimlovisertib is assessed in a whole cell functional VEGF2R assay (PAE-KDR cell line). No activity is observed at concentrations up to and including 30 μM. In a voltage clamp assay, Zimlovisertib inhibits hERG current by 25% at 100 μM.
The ability of Zimlovisertib to inhibit five major CYP450 enzymes is assessed using pooled human liver microsomes and probe substrates for the CYP450 enzymes. At a concentration of 3 μM of Zimlovisertib, less than 5% inhibition of CYPs 1A2, 2C8, 2C9, 2D6, and 3A4 is observed. Lactam Zimlovisertib is examined for time dependent inhibition effects on six major CYP450 enzymes (CYP1A2, 2B6, 2

Zimlovisertib (0.3-30 mg/kg; oral administration; for 2.5 hours; male Sprague-Dawley rats) treatment significantly inhibits LPS-induced TNF-α in a dose dependent manner. Mean exposures of Zimlovisertib in plasma are 2.1 nM, 7.7 nM, 19 nM and 150 nM free, respectively, at 2.5 hours after oral administration of Zimlovisertib at 0.3, 1, 3, and 30 mg/kg. The fraction unbound in rat plasma of Zimlovisertib is 0.3. has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[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 Fragmen
[2]. Seganish WM. Inhibitors of interleukin-1 receptor-associated kinase 4 (IRAK4): a patent review (2012-2015). Expert Opin Ther Pat. 2016 Aug;26(8):917-32.

In Vitro: DMSO : 62.5 mg/mL (172.95 mM; ultrasonic and warming and heat to 60°C)配制储备液