生物活性

Copanlisib is a highly potent pan-type I PI3K inhibitor, with IC50 values of 0.5, 3.7, 6.4, and 0.7 nM for PI3Kα/β/γ/δ inhibition, respectively. It is currently in Phase 3 development. This product has poor solubility and is suitable for animal experiments, but caution should be exercised when selecting it for cell experiments。

体外研究

BAY 80-6946 is a PI3K inhibitor with antitumor activity. BAY 86-9766 inhibits the proliferation of HuCCT-1 (KRASG12D) and EGI-1 (KRASG12D) cell lines, with IC50 values of 147 nM and 137 nM, respectively.

体内研究

激酶实验

The biochemical assay for detecting p110α involves a radiometric assay that measures the extent to which 33P permeates into the p110α substrate, phosphatidylinositol (PI). His-tagged N-terminally truncated (ΔN 1-108) p110α and similarly truncated p110β lacking the p85 binding domain (ΔN 1-108) proteins were expressed in Sf9 cells and purified to over 50% purity. To obtain IC50 values, reactions were conducted in 384-well plates using MaxiSorp plates under the following conditions. Each well was coated with a mixture of phosphatidylinositol (PI) and phosphatidylserine (PS) at a molar ratio of 1:1, diluted in chloroform. The plates were placed in a fume hood overnight to evaporate the organic solution. The plates were sealed and stored at 4°C for 1 month. Each well was treated with 7.5 ng of truncated p110α protein, and each well contained 9 μL of assay buffer (50 mM MOPSO pH 7.0, 100 mM NaCl, 4 mM MgCl2, 0.1% (w/v) BSA), except for the control group, which contained only assay buffer. 1 μL of test compound dissolved in DMSO was transferred from the dilution to obtain an 8-point dose response (0.0, 0.003, 0.01, 0.03, 0.1, 0.3, 1.0, 3.0, and 10 μM final concentration of BAY compound). A 40 μM ATP solution containing 20 μCi/mL [γ-33P]-ATP was added to initiate the reaction, which was gently mixed at room temperature for 2 hours. The reaction was terminated by adding 5 μL of 25 mM EDTA stock solution. Instead of washing the plates with detergent, a 384-well plate washer was used, and then 25 μL of UltimaGold scintillation cocktail was added to each well. The radioactivity permeating into the immobilized PI substrate was measured using a BetaPlate liquid scintillation counter.

细胞实验

动物实验

不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）

例如，已知某工具药用于小鼠的剂量为88 mg/kg , 则用于大鼠的剂量换算方法：将88 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到该药物用于大鼠的等效剂量44 mg/kg。

参考文献

1. BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110α and p110δ activities in tumor cell lines and xenograft models.2013 Nov;12(11):2319-30
2.A preclinical evaluation of the PI3K alpha/delta dominant inhibitor BAY 80-6946 in HER2-positive breast cancer models with acquired resistance to the HER2-targeted therapies trastuzumab and lapatinib.2015 Jan;149(2):373-83.

体内溶解度

Clinical Trial Information ( data from http://clinicaltrials.gov )

注：以上所有数据均来自公开文献，并不保证对所有实验均有效，数据仅供参考。

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