Idelalisib

870281-82-6

C22H18FN7O

DMSO : >= 59.7 mg/mL (143.71 mM)

PI3K/Akt/mTOR; Autophagy

Idelalisib (CAL-101) is a highly selective and orally bioavailable p110delta inhibitor with an IC₅₀ of 2.5 nM, showing 40- to 300-fold selectivity for p110delta over other PI3K class I enzymes. IC50 & Target: IC50: 2.5 nM (p110delta), 89 nM (p110gamma), 565 nM (p110beta), 820 nM (p110alpha)^[1] In Vitro: Idelalisib (CAL-101) is a highly selective and potent p110delta inhibitor (EC₅₀=8 nM). Greater selectivity (400- to 4000-fold) is seen against related kinases C2beta, hVPS34, DNA-PK, and mTOR, whereas no activity is observed against a panel of 402 diverse kinases at 10 uM. CAL-101 reduces PDGF-induced pAkt by only 25% at 10 uM. Idelalisib (CAL-101) inhibits LPA-induced pAkt with an EC₅₀ of 1.9 uM. Idelalisib (CAL-101) blocks FcepsilonRI p110delta-mediated CD63 expression with an EC₅₀ of 8 nM, whereas formyl-methionyl-leucyl-phenylalanine activation of p110gamma is inhibited with an EC₅₀ of 3 uM. Thus, in cell-based assays, CAL-101 has 240- to 2500-fold selectivity for p110delta over the other class I PI3K isoforms^[1]. CAL-101Idelalisib (CAL-101)-induced apoptosis of chronic lymphocytic leukemia (CLL) cells is significant compare with vehicle treatment alone (P<0.001). Idelalisib (CAL-101) induces selective cytotoxicity in CLL cells independent of IgVH mutational status or interphase cytogenetics^[2]. In Vivo: A significant reduction is observed in the CD11b⁺Ly6G⁺ neutrophils from brain homogenates of bothp110delta^D910A/D910A mice and Idelalisib (CAL-101) (40 mg/kg, i.v.) post-treated mice^[3].