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Duvelisib

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Chemical Structure| 1201438-56-3 同义名 : IPI-145;INK1197
CAS号 : 1201438-56-3
货号 : A270608
分子式 : C22H17ClN6O
纯度 : 99%+
分子量 : 416.863
MDL号 : MFCD15144635
存储条件：

粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 40 mg/mL(95.95 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • p110γ

    PI3Kγ, Ki:243 pM

  • p110β

    PI3Kβ, Ki:1564 pM

  • p110δ

    PI3Kδ, Ki:23 pM
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]
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT02158091 Chronic Lymphocytic Leukemia Phase 1 Phase 2 Active, not recruiting July 2021 United States, Massachusetts ... 展开 >> Beth Isreal Deaconess Medical Center Boston, Massachusetts, United States, 02115 Dana Farber Cancer Institute Boston, Massachusetts, United States, 02115 收起 <<
NCT01925911 Healthy Phase 1 Completed - United States, Kansas ... 展开 >> PRA International Lenexa, Kansas, United States, 66219 收起 <<
NCT03757000 B-cell Lymphoma Recurrent ... 展开 >> B-cell Chronic Lymphocytic Leukemia 收起 << Phase 1 Recruiting May 30, 2019 China, Beijing ... 展开 >> Peking Cancer Hospital Recruiting Beijing, Beijing, China, 100142 Contact: Yuqin Song, MD,PhD    86 10-88140650    songyuqin622@163.com    Contact: Meifeng Tu, MD,PhD    86 10-88121122    44329472@qq.com    Principal Investigator: Yuqin Song, MD,PhD          Sub-Investigator: Meifeng Tu, MD,PhD          Sub-Investigator: Lingyan Ping, MD,PhD          China, Jiangsu Jiangsu Province Hospital Not yet recruiting Nanjing, Jiangsu, China, 210029 Contact: Jiangyong Li, MD,PhD    86 25-83714511    lijianyonglm@126.com    Contact: Wei Xu, MD,PhD    86 25-83714511    xuwei0484@jsph.org.cn    Principal Investigator: Jianyong Li, MD,PhD          Sub-Investigator: Meifeng Tu, MD,PhD          China, Tianjin Hematology Hospital of Chinese Academy of Medical Sciences Recruiting Tianjin, Tianjin, China, 300020 Contact: Lugui Qiu, MD,PhD    86 22-23909172    qiulg@ihcams.ac.cn    Contact: Junyuan Qi, MD,PhD    86 22-23909999    qijy@ihcams.ac.cn    Principal Investigator: Lugui Qiu, MD,PhD          Sub-Investigator: Junyuan Qi, MD,PhD 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.40mL

0.48mL

0.24mL

11.99mL

2.40mL

1.20mL

23.99mL

4.80mL

2.40mL
参考文献

[1]Winkler DG, Faia KL, et al. PI3K-δ and PI3K-γ inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol. 2013;20(11):1364-74

[2]Zhao HF, Wang J, et al. Recent advances in the use of PI3K inhibitors for glioblastoma multiforme: current preclinical and clinical development. Mol Cancer. 2017 Jun 7;16(1):100.

[3]Winkler DG, Faia KL, et al. PI3K-δ and PI3K-γ inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol. 2013 Nov 21;20(11):1364-74.

[4]Chen SS, Ham S, et al. Dual Inhibition of PI3K-Delta and Gamma By Duvelisib (IPI-145) Impairs CLL B- and T-Cell Migration, Survival and Proliferation in a Murine Xenograft Model Using Primary Chronic Lymphocytic Leukemia Cells. Blood. vol. 126 no. 23 1753.

[5]Vangapandu HV, Jain N, et al. Duvelisib: a phosphoinositide-3 kinase δ/γ inhibitor for chronic lymphocytic leukemia. Expert Opin Investig Drugs. 2017 May;26(5):625-632.