PF-06650833

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. PF-06650833 is used to treat diseases such as rheumatoid arthritis, lupus, and lymphomas.

Product information

CAS Number: 1817626-54-2

Molecular Weight: 361.37

Formula: C18H20FN3O4

Chemical Name: 1-{[(2S,3S,4S)-3-ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-7-methoxyisoquinoline-6-carboxamide

Smiles: COC1=CC2=C(C=C1C(N)=O)C=CN=C2OC[C@H]1NC(=O)[C@@H](F)[C@H]1CC

InChiKey: JKDGKIBAOAFRPJ-ZBINZKHDSA-N

InChi: InChI=1S/C18H20FN3O4/c1-3-10-13(22-17(24)15(10)19)8-26-18-11-7-14(25-2)12(16(20)23)6-9(11)4-5-21-18/h4-7,10,13,15H,3,8H2,1-2H3,(H2,20,23)(H,22,24)/t10-,13+,15-/m0/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : ≥ 100 mg/mL (276.72 mM).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

The kinome selectivity profile of PF-06650833 (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 PF-06650833 (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, PF-06650833 inhibits hERG current by 25% at 100 μM. The ability of PF-06650833 (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 PF-06650833, less than 5% inhibition of CYPs 1A2, 2C8, 2C9, 2D6, and 3A4 is observed. Lactam PF-06650833 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 PF-06650833, no time dependent CYP inhibition is observed. The potential induction of CYP3A by PF-06650833 is assessed using cryopreserved human hepatocytes and afforded a 4.4-fold increase in mRNA at 10 μM.

In Vivo:

PF-06650833 (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 PF-06650833 in plasma are 2.1 nM, 7.7 nM, 19 nM and 150 nM free, respectively, at 2.5 hours after oral administration of PF-06650833 at 0.3, 1, 3, and 30 mg/kg. The fraction unbound in rat plasma of PF-06650833 is 0.3.

Products are for research use only. Not for human use.