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PF06650833 (Synonyms: PF-06650833)

Catalog No.GC19287

PF06650833 (PF-06650833) is a potent, selective and orally active inhibitor of interleukin-1 receptor associated kinase 4 (IRAK4) with IC50s of 0.2 and 2.4 nM in the cell and PBMC assay, respectively.

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PF06650833 Chemical Structure

Cas No.: 1817626-54-2

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5mg
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10mg
$88.00
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50mg
$388.00
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100mg
$663.00
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Sample solution is provided at 25 µL, 10mM.

Product Documents

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Background

PF06650833 is a potent, selective and orally active inhibitor of interleukin-1 receptor associated kinase 4 (IRAK4) with IC50s of 0.2 and 2.4 nM in the cell and PBMC assay, respectively. PF06650833 is used to treat diseases such as rheumatoid arthritis, lupus, and lymphomas[1][2].

The kinome selectivity profile of PF06650833 (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[1]. Lactam PF06650833 (Compound 40) 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, PF06650833 inhibits hERG current by 25% at 100 μM[1]. The ability of PF06650833 (Compound 40) 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 PF06650833, less than 5% inhibition of CYPs 1A2, 2C8, 2C9, 2D6, and 3A4 is observed. Lactam PF06650833 is examined for time dependent inhibition effects on six major CYP450 enzymes (CYP1A2, 2B6, 2C8, 2C9, 2C19, and 2D6) using pooled human liver microsomes and probe substrates. At 100 μM of PF06650833, no time dependent CYP inhibition is observed. The potential induction of CYP3A by PF06650833 is assessed using cryopreserved human hepatocytes and afforded a 4.4-fold increase in mRNA at 10 μM[1].

PF06650833 (Compound 40; 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 PF06650833 in plasma are 2.1 nM, 7.7 nM, 19 nM and 150 nM free, respectively, at 2.5 hours after oral administration of PF06650833 at 0.3, 1, 3, and 30 mg/kg. The fraction unbound in rat plasma of PF06650833 is 0.3[1].

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.
[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.

Chemical Properties

Cas No. 1817626-54-2 SDF
Synonyms PF-06650833
Canonical SMILES NC(C1=C(OC)C=C2C(C=CN=C2OC[C@@H]3[C@H](CC)[C@H](F)C(N3)=O)=C1)=O
Formula C18H20FN3O4 M.Wt 361.37
Solubility DMSO : ≥ 33 mg/mL (91.32 mM) Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 2.7672 mL 13.8362 mL 27.6725 mL
5 mM 0.5534 mL 2.7672 mL 5.5345 mL
10 mM 0.2767 mL 1.3836 mL 2.7672 mL
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Average Rating: 5 ★★★★★ (Based on Reviews and 40 reference(s) in Google Scholar.)

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