Tubulin/HDAC-IN-1 是一种双重的tubulin和HDAC-IN-1抑制剂，其通过与 tubulin 的 CH/π 相互作用以及与 HDAC8 的氢键相互作用而发挥功能。Tubulin/HDAC-IN-1 可抑制 tubulin 聚合并选择性抑制 HDAC8 (IC50: 150 nM)。Tubulin/HDAC-IN-1 对各种人类癌细胞具有细胞毒性，还可将细胞周期阻滞在 G2/M 期并诱导细胞凋亡 (apoptosis)。Tubulin/HDAC-IN-1 可用于神经母细胞瘤、白血病等血液肿瘤和实体肿瘤的研究。
| 生物活性 | Tubulin/HDAC-IN-1 is a dualtubulinandHDAC-IN-1inhibitor through CH/π interaction with tubulin and hydrogen bond interaction withHDAC8. Tubulin/HDAC-IN-1 inhibits tubulin polymerization and selectively inhibitsHDAC8(IC50: 150 nM). Tubulin/HDAC-IN-1 has cytotoxicity against various humancancercells, also arrests cell cycle in the G2/M phase and induces cellapoptosis. Tubulin/HDAC-IN-1 can be used in the research of hematologic and solid tumors such as neuroblastoma, leukemia[1]. |
| IC50& Target[1] | HDAC8 150 nM (IC50) | HDAC6 1 μM (IC50) | HDAC11 1.9 μM (IC50) |
|
体外研究
(In Vitro) | Tubulin/HDAC-IN-1 (Compound 12a, 72 h) shows cytotoxicity against various human cancer cell lines with an averaged IC50value of 0.6 nM[1].
Tubulin/HDAC-IN-1 (2 nM, 24 h) induces HT29 cell cycle arrest in the G2/M phase and produces caspase-induced apoptosis of HT29 cells through mitochondrial dysfunction[1].
Tubulin/HDAC-IN-1 selectively inhibits HDAC8 (IC50: 150 nM), inhibits HDAC6 and HDAC11 with IC50values of 1 μM and 1.9 μM respectively[1].
Tubulin/HDAC-IN-1 (0.5-100 nM, 24 h/30 min) dose-dependently increases γH2AX level and acetylated SMC3 in HT-29 cells[1].
Tubulin/HDAC-IN-1 (5-15 μΜ, 0-40 min) inhibits tubulin polymerization in a dose-dependent manner, with a maximal effect achieved at 10 μM[1].
Tubulin/HDAC-IN-1 (250 nM, 30 min) depolymerizes the cell microtubule network, and the effect is not specific[1].
Tubulin/HDAC-IN-1 shows goodin vitrometabolic stability expressed by the intrinsic clearance CLint (given in μL/min/mg protein) using rat liver microsomes (RLM) and human liver microsomes (HLM)[1].
| Compound | RLM | RLM | HLM | HLM | | t1/2(h) | CLint | t1/2 | CLint | | Tubulin/HDAC-IN-1 | 6.6 | 1.75 | 32 | 0.36 |
Cell Proliferation Assay[1] | Cell Line: | Various tumor cell lines as below | | Concentration: | | | Incubation Time: | 72 h | | Result: | Activities of Tubulin/HDAC-IN-1 (Compound 12a) against various tumor cell lines (IC50nM):
| NCIN87 | K562 | K562R | MiaPaca2 | SKOV3 | A549 | MCF-7 | MDA-MB-231 | HCT116 | HT-29 | | Tubulin/HDAC-IN-1 | 0.1 | 0.35 | 0.56 | 0.94 | 0.6 | 0.84 | 0.78 | 0.7 | 0.6 | 0.62 |
|
Western Blot Analysis[1] | Cell Line: | HT-29 cells | | Concentration: | 0.5, 1, 5, 10 nM for γH2AX; 0.5, 1, 100 nM for acetylated SMC3 | | Incubation Time: | 24 h for γH2AX, 30 min for acetylated SMC3 | | Result: | Dose-dependently increased γH2AX level and acetylated SMC3. |
|
体内研究
(In Vivo) | Tubulin/HDAC-IN-1 (Compound 12a, intratumoral injection, 0.25 mg/kg, three times a week for two weeks) decreases MCA205 tumor growth and extends the overall survival of treated mice in allogeneic sarcoma mice model[1].
| Animal Model: | Allogeneic sarcoma model in C57BL/6 mice[1] | | Dosage: | 0.1, 0.25, 0.50 mg/kg, three times a week for two weeks. | | Administration: | Intratumoral injection | | Result: | Decreased tumor growth and extended the overall survival of treated mice with no obvious side effects. |
|
| 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. |
