| 生物活性： |
靶点：PI3K
通路：PI3K/Akt/mTOR
背景说明：是一种具有高度选择性的、有效的p110δ抑制剂。
生物活性：Acalisib is a potent and selective PI3Kδ inhibitor with an IC50 of 12.7 nM.[1-2]
In Vitro：Acalisib(GS-9820)is more selective for PI3Kδ(IC50=12.7 nM)relative to other PI3K class I enzymes(IC50: PI3Kα，5，441 nM; PI3Kβ，3，377 nM; PI3Kγ，1，389 nM). Acalisib is also 103-fold more selective against PI3Kδ than against related kinases，such as PI3KCIIβ(IC50>10 nM)，hVPS34(IC50=12.7 μM)，DNA-PK(IC50=18.7 μM)，and mTOR(IC50>10 nM). In fibroblasts，the PDGF receptor signals through PI3Kα and the GPCR for lysophosphatidic acid(LPA)signals through PI3Kβ. Acalisib reduces PDGF-induced pAkt by only 50% at 11，585 nM，and LPA-induced pAkt by 50% at 2，069 nM.[1]
In Vivo：To dissect the relative contribution of PI3Kα and PI3Kδ inhibition in the reduction of obesity，obese hyperphagic ob/ob mice are treated with a selective PI3Kα inhibitor，BYL-719，or with a selective PI3Kδ inhibitor，Acalisib(GS-9820). Remarkably，BYL-719 reduces body weight after 15 days of treatment to a similar extent as CNIO-PI3Ki，whereas Acalisib has no significant effect at the same doses as BYL-719. It should be noted that 10 mg/kg of Acalisib is sufficient to reduce the growth of multiple myeloma xenografts in mice[2].
细胞实验：The effect of inhibitors on RAW264.7 cell survival is evaluated using the MTT assay. RAW264.7 cells are seeded in Falcon flat bottom 96-well plates at a density of 2.5-3×104 cells/cm2 in 100 μL of DMEM with 10% FBS and 1% antibiotic solution. After seeding，the cells are allowed to attach for 24 h then exposed to control or Acalisib(GS-9820)(100 pM to 10 μM)for 24 h. After incubation at 37°C in 5% CO2，MTT substrate is added at a final concentration of 0.5 mg/mL for 4 h. Following a 4-h incubation，100 μL of solubilization solution is added to each well to dissolve the formazan crystals and samples are analyzed after 24 h. Absorbance of the samples is assessed using a plate reader using a wavelength of 550 nm and a reference wavelength of 700 nm[1].
动物实验：Ob/ob C57BL6J mice and Wild-type C57BL6J/Ola.Hsd mice are housed under specific pathogen free(SPF)conditions，at 22°C，and with 12 hours dark/light cycles(light cycle from 8 am to 8 pm). All mice used are males of 20 weeks of age. Mice are fed with standard chow diet(18% of fat-based caloric content). PI3K inhibitors are administered daily by oral gavage during 15 or 16 days as follows，BYL-719(5 and 10 mg/kg)and Acalisib(5 and 10 mg/kg)，CNIO-PI3Ki(1 and 5 mg/kg)，dissolved in PEG-300 and 10% N-methyl-2-pyrrolidone.[2]
激酶实验：Biochemical in vitro lipid kinase assays are performed. A stock solution of Acalisib(GS-9820)is prepared in DMSO at a concentration of 10 mM. Ten-point kinase inhibitory activities are measured over a concentration range(5 to 104 nM)with ATP at a concentration consistent with the Km of each of the enzymes[1].
数据来源文献：[1]. Shugg RP， et al. Effects of isoform-selective phosphatidylinositol 3-kinase inhibitors on osteoclasts: actions on cytoskeletal organization， survival， and resorption. J Biol Chem. 2013 Dec 6;288(49):35346-57.
[2]. Lopez-Guadamillas E， et al. PI3Kα inhibition reduces obesity in mice. Aging (Albany NY). 2016 Nov 4;8(11):2747-2753
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| 其它标识： |
EC：EINECS 604-604-1
SMILES：O=C1N(C2=CC=CC=C2)C([C@@H](NC3=C4N=CNC4=NC=N3)C)=NC5=C1C=C(F)C=C5
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| 基本信息： |
CAS：870281-34-8
英文名称：Acalisib
别名：GS-9820;CAL-120
分子式：C21H16FN7O
分子量：401.4
规格：5mg ; 2mg
溶解性：Soluble in DMSO ≥5mg/mL(Need ultrasonic)
纯度：≥98%
外观(性状)：White to off-white Solid
储存条件：Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year
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| 靶点： |
PI3K |
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