中文名称:
2-[(1S)-1-[(2-氨基-9H-嘌呤-6-基)氨基]乙基]-5-甲基-3-(2-甲基苯基)-4(3H)-喹唑啉酮盐酸盐
中文同义词:
2-[(1S)-1-[(2-氨基-9H-嘌呤-6-基)氨基]乙基]-5-甲基-3-(2-甲基苯基)-4(3H)-喹唑啉酮盐酸盐;PI3K抑制剂(CAL-130 HYDROCHLORIDE)
英文名称:
(S)-2-(1-((2-aMino-9H-purin-6-yl)aMino)ethyl)-5-Methyl-3-(o-tolyl)quinazolin-4(3H)-one hydrochloride
英文同义词:
(S)-2-(1-((2-aMino-9H-purin-6-yl)aMino)ethyl)-5-Methyl-3-(o-tolyl)quinazolin-4(3H)-one hydrochloride;CAL-130 (Hydrochloride);2-[(1S)-1-[(2-Amino-9H-purin-6-yl)amino]ethyl]-5-methyl-3-(2-methylphenyl)-4(3H)-quinazolinone hydrochloride (1:1);CAL-130 HCl
生物活性
CAL-130 Hydrochloride 是一种 PI3Kδ 和 PI3Kγ 抑制剂，IC50 分别为 1.3 和 6.1 nM。
靶点
p110δ
1.3 nM (IC 50 )
p110γ
6.1 nM (IC 50 )
p110β
56 nM (IC 50 )
p110α
115 nM (IC 50 )
p110δ
1.3 nM (IC 50 )
p110γ
6.1 nM (IC 50 )
体外研究
CAL-130 preferentially inhibits the function of both p110γ and p110δ catalytic domains. IC 50 values of CAL-130 are 1.3 and 6.1 nM for p110δ and p110γ, respectively, as compared to 115 and 56 nM for p110α and p110β. CAL-130 does not inhibit additional intracellular signaling pathways (i.e., p38 MAPK or insulin receptor tyrosine kinase) that are critical for general cell function and survival.
体内研究
The clinical significance of interfering with the combined activities of PI3Kγ and PI3Kδ is determined by administering CAL-130 to Lck/Pten fl/fl mice with established T cell acute lymphoblastic leukemia (T-ALL). Candidate animals for survival studies are ill appearing, have a white blood cell (WBC) count above 45,000 μL -1 , evidence of blasts on peripheral smear, and a majority of circulation cells (>75%) staining double positive for Thy1.2 and Ki-67. Mice receive an oral dose (10 mg/kg) of CAL-130 every 8 hr for a period of 7 days and are then followed until moribund. Despite the limited duration of therapy, CAL-130 is highly effective in extending the median survival for treated animals to 45 days as compared 7.5 days for the control group.
