CDK6/PIM1-IN-1 是一种有效且平衡的双重CDK6/PIM1抑制剂，IC50分别为 39 nM 和 88 nM。CDK6/PIM1-IN-1 抑制 CDK4 (IC50=3.6 nM)。CDK6/PIM1-IN-1 可显著抑制急性髓系白血病 (AML) 细胞增殖，将细胞周期阻滞在 G1 期，并促进细胞凋亡。CDK6/PIM1-IN-1 具有抗AML活性。
| 生物活性 | CDK6/PIM1-IN-1 is a potent and balanced dualCDK6/PIM1inhibitor withIC50 values of 39 and 88 nM, respectively. CDK6/PIM1-IN-1 inhibitsCDK4(IC50=3.6 nM). CDK6/PIM1-IN-1 significantly inhibits acute myeloid leukemia (AML) cell proliferation, arrest cell cycle at the G1 phase, and promote cellapoptosis. CDK6/PIM1-IN-1 exhibits potent anti-AML activity[1].
|
| IC50& Target[1] | CDK6/cyclinD1 39 nM (IC50) | PIM1 88 nM (IC50) | CDK1/cyclinB >10 μM (IC50) | CDK2/cyclinA 2.274 μM (IC50) | CDK3/Cyclin E >10 μM (IC50) | Cdk4/cyclin D1 3.6 nM (IC50) | Cdk5/p25 >10 μM (IC50) | CDK7/Cyclin H/MNAT1 393 nM (IC50) | CDK9/cyclinT1 440 nM (IC50) | CDK12/Cyclin K >10 μM (IC50) | CDK13/Cyclin K >10 μM (IC50) | PIM2 >10 μM (IC50) | PIM3 92 nM (IC50) |
|
体外研究
(In Vitro) | CDK6/PIM1-IN-1 (compound 51) exhibits more than 10 times selectivity over CDK1 (IC50>10 μM), CDK2 (IC50=2.274 μM), CDK3 (IC50>10 μM), CDK5 (IC50>10 μM), CDK7 (IC50=393 nM), CDK9 (IC50=440 nM), CDK12 (IC50>10 μM), and CDK13 (IC50>10 μM). CDK6/PIM1-IN-1 shows inhibitory activity against PIM2 (IC50>10 μM) and PIM3 (IC50=92 nM)[1].
CDK6/PIM1-IN-1 inhibits proliferation in AML cells (K562 cell,GI50=1.026 μM; HL-60 cell,GI50=1.069 μM; MOLM13 cell, GI50=1.362 μM)[1].
CDK6/PIM1-IN-1 (0.5, 1, 1.5 μM) causes a G1 arrest in a dose-dependent manner in K562 and HL-60 cell lines[1].
CDK6/PIM1-IN-1 (1, 2, 4 μM) promotes the apoptosis of K562 and HL-60 cell lines in a dose-dependent manner[1].
CDK6/PIM1-IN-1 (0.5, 1, 1.5 μM; for 24 h) reduces p-retinoblastoma (RB) and p-BAD levels in a concentration-dependent manner. CDK6/PIM1-IN-1 decreases the PIM1 level[1].
|
体内研究
(In Vivo) | CDK6/PIM1-IN-1 (compound 51; orally; 60, 90 mg/kg/day; 17 days) displays more potent antitumor activity in BALB/c mice with K562 cell lines[1].
CDK6/PIM1-IN-1 (iv; 5 mg/kg) has the t1/2, MRT0-∞, and AUC0-∞ values of 9.78 h, 14.61 h, and 1153.74 h·ng/mL, respectively in Sprague–Dawley (SD) rats[1].
CDK6/PIM1-IN-1 (po; 5 mg/kg) has the t1/2, Tmax, Cmax, and AUC0-∞of 15.81 h, 11 h, 152.31 ng/mL, and 5152.92 h·ng/mL, respectively in SD rats[1].
|
| 分子量 | |
| Formula | |
| CAS 号 | |
| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
m.cnreagent.com