生物活性

• 靶点

  PI3Kγ IC50:50nM

  PI3Kδ IC50:1nM

• 描述PI3Ks are lipid kinases participating in several cellular process. There are eight PI3 kinases have been identified as classes IA, 1B, II, and III based on the sequence homology and substrate preference. Among them, class IA PI3K is composed of a heterodimer consisting of a 110 kDa catalytic subunit (p110α, p110β and p110δ) and an 85 kDa regulatory subunit ^[2]. Duvelisib, also called IPI-145 or INK1197, is an oral and selective PI3K δ/γ inhibitor with Ki and IC50 of 23 pM/240 pM and 2.5nM/27nM, respectively, and is less potent to PI3K-α and PI3K-β with Ki and IC50 of 25.9nM/1.56nM and 1602nM/85nM (by recombinant PI3K isoforms), respectively. Through inhibition of PI3K-δand PI3K-γ function, Duvelisib can decrease pS473-Akt in RAJI/RAW 264.7/SKOV-3 cells as well as inhibit the proliferation of Primary B/T cells, PI3K-δ-specific degranulation of basophils and the activated GPIIb/IIIa in platelets. In animal study, Duvelisib is used in inflammatory, autoimmune and hematologic diseases model. For example, 10 mg/kg treatment of IPI-145 can suppress cellular inflammation in an OVA-induced asthma rat model with significant suppression of TNF-a, KC/GRO, interleukin-13 (IL-13) and IL-5 levels in bronchoalveolar lavage ^[1], and also effective in a murine xenograft model of CLL^[3]. Up to now, Duvelisib is FDA approved for use in combination with rituximab for the treatment of relapsed chronic lymphocytic leukemia (CLL) and follicular lymphoma ^[4].
• 作用机制IPI-145 is an ATP-competitive inhibitor. ^[1]

• 动物研究
  剂量	Mice: min = 10 mg/kg[4], max = 50 mg/kg bid[5]
  给药途径	p.o.