1276105-89-5
基本信息
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
CNX-1351
CNX-1351, >=98%
CNX-1351
CNX 1351
CNX1351
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
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-(4-morpholinyl)thieno[3,2-d]pyrimidin-6-yl]methyl]-1-piperazinyl]-6-methyl-5-heptene-1,4-dione CNX1351
物理化学性质
| 密度 | 1.328±0.06 g/cm3(Predicted) |
| 储存条件 | -20°C储存 |
| 溶解度 | DMSO : 33.33 mg/mL (58.10 mM; Need ultrasonic) |
| 酸度系数(pKa) | 12.22±0.40(Predicted) |
| 形态 | 粉末 |
| 颜色 | White to yellow |
安全数据
| 危险性符号(GHS) |  GHS07 |
| 警示词 | 警告 |
| 危险性描述 | H315-H319 |
| 防范说明 | P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313 |
常见问题列表
|
PI3Kα 6.8 nM (IC 50 ) |
PI3Kβ 166 nM (IC 50 ) |
PI3Kδ 240.3 nM (IC 50 ) |
PI3Kγ 3020 nM (IC 50 ) |
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).
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.