| Synonyms |
CAL101, GS-1101, GS1101, GS 1101, CAL 101, Idelalisib |
| Biological Description |
CAL-101 is a highly selective and potent p110delta inhibitor with IC50 of 2.5 nM, is 40- to 300-fold more selective for p110delta relative to other PI3K class I enzymes (p110alpha, p110beta, and p110gamma; IC50 are 820, 565, and 89nM, respectively).
IC50 & Target: IC50: 2.5 nM (p110delta), 89 nM (p110gamma), 565 nM (p110beta), 820 nM (p110alpha)[1]
In Vitro: 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. CAL-101 inhibits LPA-induced pAkt with an EC50 of 1.9 uM. 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-101-induced apoptosis of chronic lymphocytic leukemia (CLL) cells is significant compare with vehicle treatment alone (P<0.001). 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 bothp110deltaD910A/D910A mice and CAL-101 (40 mg/kg, i.v.) post-treated mice[3]. |
