PI3kδ inhibitor 1 

PI3kδ inhibitor 1 is a potent and selective PI3Kδ inhibitor with an IC₅₀ of 3.8 nM.

PI3kδ inhibitor 1 (Compound 3) is a potent inhibitor of PI3Kδ that is 200-400 fold selective for all three remaining Class I PI3K isoforms and extremely selective relative to 239 kinases tested in SelectScreen service (0/239 kinases showing >50% inhibition when tested at 1 μM; mTOR, DNA-PK, VPS34, PI4Kα and PI4Kβ are inhibited at 10% or less when tested at 1 μM; PIKC2A and PIKC2B are inhibited at 11% and 42%, respectively, at this same concentration and show less than 10% inhibition when tested at 0.1 μM; the PIKK family kinases ATM and ATR are not assessed)^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

The pharmacokinetic properties of PI3kδ inhibitor 1 (Compound 3) are evaluated in mice and rats when dosed IV and orally. Good plasma exposures and reasonable half-lives are observed upon oral dosing, a reflection of high oral bioavailability (80% and 90% at a low dose for mouse and rat, respectively), moderate volume of distribution, and moderate clearance. PI3kδ inhibitor 1 has moderate terminal elimination half-life (t_1/2=2.6 h, 2.9 h, 5 h, 2.6, 3.8 and 4.8 h for mouse (5 mg/kg, po), mouse (20 mg/kg, po), mouse (40 mg/kg, po), rat (5 mg/kg, po), rat (10 mg/kg, po), rat (30 mg/kg, po)). Plasma exposures and Cmax levels increase with dose in both mice and rats, important in that inflammatory disease models utilize these two species. Plasma protein binding for PI3kδ inhibitor 1 ranges from 80-88% in rodents and is consistent with values obtained in human plasma (86%)^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

504.60

C₂₈H₃₃FN₆O₂

1332075-63-4

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Sutherlin DP, et al. Potent and selective inhibitors of PI3Kδ: obtaining isoform selectivity from the affinity pocket and tryptophan shelf. Bioorg Med Chem Lett. 2012 Jul 1;22(13):4296-302.  [Content Brief]