生物活性

• 靶点

  p110α IC50:820nM

  p110β IC50:565nM

  p110γ IC50:89nM

  p110δ IC50:2.5nM

• 描述PI3Ks are lipid kinases participating in several cellular process. There are eight PI3Ks, which have been identified as classes IA, 1B, II and III based on the sequence homology and substrate preference. The class IA PI3K is a heterodimer consisting of a 110 kDa catalytic subunit (p110α, p110β and p110δ), and an 85 kDa regulatory subunit^[2]. CAL-101 is an orally available and selective inhibitor of p110δ (IC50=2.5nM, analyzed using the SelectScreen kinase inhibitor assay service) with less potent to p110γ (IC50=89nM). In SU-DHL-5, KARPAS-422 and B-ALL (CCRF-SB) cell lines, CAL-101 can produce a concentration-dependent reduction in pAktS473, pAktT308 and the downstream target S6 and also induce apoptosis significantly^[1]. It has also been found that CAL-101 can induce caspase-dependent death of malignant CLL cells, suppresse the production of protumor cytokine by T and NK cells, as well as abrogate prosurvival microenvironmental signals like B-cell activating factor, tumor necrosis factor and fibronectin^[3]. Thus, CAL-101 has effects both on tumor microenvironment and directly on tumors. Now CAL-101 has been used in monotherapy studies in patients with non-Hodgkin lymphoma (Phase1/2)^[4].
• 作用机制Idelalisib can bind to the ATP-binding pocket of PI3Kδ, which is responsible for the selectivity for PI3Kδ.^[5]

• 动物研究
  剂量	Mice: min = 10 mg/kg[6], max = 40 mg/kg[7]
  给药途径	p.o, i.v, i.p