上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白，专注于信号通路和疾病研究领域。
HDAC1/2 and CDK2-IN-1 (compound 14d) 是一种有效的 HDAC1，HDAC2 和 CDK2 抑制剂，IC50 分别为 70.7，23.1 和 0.80 μM。HDAC1/2 and CDK2-IN-1 可阻断细胞周期，诱导细胞凋亡 (apoptosis)。HDAC1/2 and CDK2-IN-1 表现出良好的体内抗肿瘤活性。
| 生物活性 |
HDAC1/2 and CDK2-IN-1 (compound 14d) is a potent HDAC1, HDAC2 and CDK2 dual inhibitor, with IC50 values of 70.7, 23.1 and 0.80 μM, respectively. HDAC1/2 and CDK2-IN-1 can block the cell cycle and induce apoptosis. HDAC1/2 and CDK2-IN-1 exhibits desirable in vivo antitumor activity[1].
|
| IC50 & Target[1] |
|
HDAC1
70.7 nM (IC50)
|
HDAC2
23.1 nM (IC50)
|
CDK2
0.80 nM (IC50)
|
|
体外研究
(In Vitro) |
HDAC1/2 and CDK2-IN-1 (compound 14d) shows excellent antiproliferative activities against H460, A375, HepG2, HCT116 and Hela cells with IC50 values of 1.59, 0.47, 0.86, 0.58 and 1.05 μM, respectively[1].
HDAC1/2 and CDK2-IN-1 (0.5 μM, 48 h) significantly inhibits the migration of H460 and A375 cells[1].
HDAC1/2 and CDK2-IN-1 (0-2 μM, 24 h) significantly blocks the cell cycle in the G2/M phase[1].
HDAC1/2 and CDK2-IN-1 (0-2 μM, 48 h) promotes cancer cell apoptosis in a dose-dependent manner[1].
HDAC1/2 and CDK2-IN-1 (1 μM, 12 h) inhibits CDK2 and HDAC activity, causing cancer cell death[1].
HDAC1/2 and CDK2-IN-1 (1 μM, 24 h) strongly increases ROS levels in A375 cells, causes cancer cell death by improving intracellular ROS levels[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Cycle Analysis
| Cell Line: |
A375, HCT116, H460 and Hela cells[1] |
| Concentration: |
0, 0.5, 1, 2 μM |
| Incubation Time: |
24 h |
| Result: |
Significantly blocked the cell cycle, induced a loss of G0/G1 phase cells and an increase of G2/M phase cells, led to an apparent accumulation of cells in G2/M phase at 0.5 μM (A375, the percentage from 13.70 to 57.03%; HCT116, from 27.46 to 76.99%; Hela, from 7.89% to 51.85%). |
Apoptosis Analysis
| Cell Line: |
A375, HCT116, H460 and Hela cell lines[1] |
| Concentration: |
0, 0.5, 1, 2 μM |
| Incubation Time: |
48 h |
| Result: |
Promoted cancer cell apoptosis in a dose-dependent manner, with the apoptosis rates of 91.99% (A375), 89.60% (HCT116), 59.10% (H460), and 22.36% (Hela) respectively at the concentration of 2 μM. |
Immunofluorescence
| Cell Line: |
A375 cells[1] |
| Concentration: |
1 μM |
| Incubation Time: |
12 h |
| Result: |
Significantly inhibited CDK2 and increased the acetylation level of histone H3, inhibited CDK2 and HDAC activity, causing cancer cell death. |
|
体内研究
(In Vivo) |
HDAC1/2 and CDK2-IN-1 (BALB/c nude mice, 0-100 mg/kg, IP, once daily for 21 days) significantly inhibits the tumor growth[1].
HDAC1/2 and CDK2-IN-1 (compound 14d) (ICR mice; 4 mg/kg, IV; 20 mg/kg, IP) exhibits desirable pharmacokinetic properties[1].
Pharmacokinetic Parameters of HDAC1/2 and CDK2-IN-1 in male ICR mice[1].
| Dose (mg/kg) |
4 |
20 |
| Administration |
IV |
IP |
| T1/2 (h) |
1.48 |
2.84 |
| Tmax (h) |
|
2 |
| Cmax (ng/mL) |
|
1360 |
| AUC0-t (ng/mL*h) |
2850 |
7240 |
| MRT0-t (h) |
0.563 |
4.54 |
| CL (mL/(min/kg)) |
23.3 |
|
| F (%) |
|
50.8 |
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: |
Male ICR mice (n = 9)[1] |
| Dosage: |
4 mg/kg (IV), 20 mg/kg (IP) |
| Administration: |
IV, IP, once (Pharmacokinetic Analysis) |
| Result: |
Exhibited desirable pharmacokinetic properties. |
| Animal Model: |
BALB/c nude mice (5-6 weeks, HCT116 xenograft model)[1] |
| Dosage: |
0, 25, 50 and 100 mg/kg |
| Administration: |
IP, once daily for 21 days |
| Result: |
Significantly inhibited the tumor growth, the tumor growth inhibitions were 28%, 40% and 44% at doses of 25, 50 and 100 mg/kg, respectively. |
|
| 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.
|
| 参考文献 |
-
[1]. Yun F, Cheng C, Ullah S, Yuan Q. Design, synthesis and biological evaluation of novel histone deacetylase1/2 (HDAC1/2) and cyclin-dependent Kinase2 (CDK2) dual inhibitors against malignant cancer. Eur J Med Chem. 2020;198:112322.
|
