ChemicalBook Product Catalog Biochemical Engineering Biochemical Reagents Agonist Inhibitors PF-06650833

PF-06650833

Product NamePF-06650833
CAS1817626-54-2
MFC18H20FN3O4
MW361.37
EINECS
MOL File1817626-54-2.mol

Chemical Properties

Boiling point	621.0±55.0 °C(Predicted)
Density	1.34±0.1 g/cm3(Predicted)
storage temp.	room temp
solubility	DMSO : ≥ 33 mg/mL (91.32 mM)
pka	13.44±0.70(Predicted)
form	powder
color	white to beige
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
InChIKey	JKDGKIBAOAFRPJ-ZBINZKHDSA-N
SMILES	C1(OC[C@@H]2[C@H](CC)[C@H](F)C(=O)N2)C2=C(C=C(C(N)=O)C(OC)=C2)C=CN=1

Safety Information

WGK Germany	WGK 3
Storage Class	11 - Combustible Solids
Hazard Classifications	Eye Irrit. 2 Skin Irrit. 2 STOT SE 3

Usage And Synthesis

Uses

Zimlovisertib (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. Zimlovisertib is used to treat diseases such as rheumatoid arthritis, lupus, and lymphomas[1][2].

Biochem/physiol Actions

PF06650833 has been studied for its use in the treatment of Waldenstrom macroglobulinemia, indicated by overproduction of IgM (immunoglobulin M)-producing lymphoplasmacytic cells.

in vivo

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^[1].

Animal Model:	Male Sprague-Dawley rats^[1]
Dosage:	0.1 mg/kg, 1 mg/kg, 3 mg/kg, 30 mg/kg
Administration:	Oral administration; for 2.5 hours
Result:	Significantly inhibited LPS-induced TNF-α in a dose dependent manner.

IC 50

IRAK4: .2 nM (IC₅₀)

storage

Store at -20°C

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. DOI:10.1021/acs.jmedchem.7b00231
[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. DOI:10.1080/13543776.2016.1202926

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