中文同义词:
1-[4-[[2-(1H-吲唑-4-基)-4-(4-吗啉基)噻吩并[3,2-D]嘧啶-6-基]甲基]-1-哌嗪基]-6-甲基-5-庚烯-1,4-二酮;PI3K ALPHA抑制剂(CNX-1351)
英文同义词:
1-[4-[[2-(1H-Indazol-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidin-6-yl]methyl]-1-piperazinyl]-6-methyl-5-heptene-1,4-dione CNX1351;CNX-1351, >=98%;CNX-1351;1-[4-[[2-(1H-Indazol-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidin-6-yl]methyl]-1-piperazinyl]-6-methyl-5-heptene-1,4-dione;1-(4-((2-(1H-indazol-4-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-6-methylhept-5-ene-1,4-dione;CS-1069;CNX-1351; CNX 1351; CNX1351
相关类别:
小分子抑制剂;小分子抑制剂，天然产物;细胞生物学试剂;Inhibitors
生物活性
CNX-1351 是一种有效的选择性 PI3Kα 抑制剂，IC50 为 6.8 nM。
靶点
PI3Kα
6.8 nM (IC 50 )
PI3Kβ
166 nM (IC 50 )
PI3Kδ
240.3 nM (IC 50 )
PI3Kγ
3020 nM (IC 50 )
PI3Kα
6.8 nM (IC 50 )
PI3Kβ
166 nM (IC 50 )
体外研究
CNX-1351 is able to potently (EC 50 <100 nM) and specifically inhibit signaling in PI3Kα-dependent cancer cell lines, and this leads to a potent antiproliferative effect (GI 50 <100 nM). CNX-1351 inhibits PI3K signaling in SKOV3 cells, with potency (EC 50 of 10-100 nM) similar to that of the pan-PI3K inhibitor. To investigate the functional consequence of inhibiting PI3Kα in cells, two cell lines with different PIK3CA activating mutations, SKOV3 ovarian cancer cells (H1047R) and MCF-7 breast cancer cells (E545K), are treated with CNX-1351 and growth is monitored. Both PIK3CA -driven cell lines are growth inhibited by exposure to CNX-1351 for 96 h (GI 50 of 78 and 55 nM, respectively).
体内研究
CNX-1351 inhibits p-Akt Ser473 in mouse spleens and bonds to PI3Kα in vivo. CNX-1351 is delivered into the intraperitoneal cavity of nude mice at 100 mg/kg once a day for 5 consecutive days (n=3 mice per group). Spleens are harvested from the mice at the indicated times after the last dose (1-24 h) and interrogated by immunoblot for P-Akt Ser473 or for PI3Kα occupancy. Inhibition of PI3K signaling is detected as a decrease in P-Akt Ser473 at 1 and 4 h after last dose.
