HDAC/Top-IN-1 是一种具有口服活性的、广谱的HDAC/Top双重抑制剂，对HDAC1、HDAC2、HDAC3、HDAC6和HDAC8的IC50分别为 0.036 μM、0.14 μM、0.059 μM、0.089 μM 和 9.8 μM。HDAC/Top-IN-1 能有效诱导 HEL 细胞凋亡 (apoptosis)，能将细胞阻滞在 S 期。
| 生物活性 | HDAC/Top-IN-1 is an orally active and panHDAC/Topdual inhibitor withIC50s of 0.036 μM, 0.14 μM, 0.059 μM, 0.089 μM and 9.8 μM forHDAC1,HDAC2,HDAC3,HDAC6andHDAC8. HDAC/Top-IN-1 efficiently inducesapoptosiswith S cell-cycle arrest in HEL cells. HDAC/Top-IN-1 has exhibits excellentin vivoantitumor efficacy[1]. |
| IC50& Target[1] | HDAC1 34 nM (IC50) | HDAC2 140 nM (IC50) | HDAC3 59 nM (IC50) | HDAC6 89 nM (IC50) | HDAC8 9.8 μM (IC50) |
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体外研究
(In Vitro) | HDAC/Top-IN-1 (compound 16j) (0-2 μM; 48 hours) exhibits remarkable inhibitory activities against the tested cell lines[1].
HDAC/Top-IN-1 (20 and 100 nM; 24 hours) dramatically increases acetyl-H3 and acetyl-H4 levels in HEL cells[1].
HDAC/Top-IN-1 (0.1 and 0.5 μM; 48 hours) effectively induces HEL cell apoptosis in a dose-dependent manner[1].
HDAC/Top-IN-1 (0.02-0.5 μM; 48 hours) arrests HEL cells at the S phase[1].
Cell Proliferation Assay | Cell Line: | MCF-7, A549, HCT116, HepG-2, K562 and HEL[1] | | Concentration: | 0-2 μM | | Incubation Time: | 48 hours | | Result: | Exhibited remarkable inhibitory activities against the tested cell lines, and IC50s of 0.68, 0.21, 0.26, 0.35 and 0.029 μM in MCF-7, A549, HCT116, HepG-2, K562 and HEL, respectively. |
Western Blot Analysis | Cell Line: | HEL[1] | | Concentration: | 20 and 100 nM | | Incubation Time: | 24 hours | | Result: | Dramatically increased in acetyl-H3 and acetyl-H4 levels. |
Apoptosis Analysis | Cell Line: | HEL[1] | | Concentration: | 0.1 and 0.5 μM | | Incubation Time: | 48 hours | | Result: | Led to 56.02% and 76.45% apoptotic cell death at concentration of 0.1 and 0.5 μM, respectively |
Cell Cycle Analysis | Cell Line: | HEL[1] | | Concentration: | 0.02, 0.1 and 0.5 μM | | Incubation Time: | 48 hours | | Result: | The ratios in the S phase were changed dramatically 9.8%, 15.4%, and 25.8% at 0.02, 0.1 and 0.5 μM, respectively. |
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体内研究
(In Vivo) | HDAC/Top-IN-1 exhibits good metabolic properties with a half-life (T1/2) of 31.49 min, and the clearance is 173.32 mL/min/mg[1].
HDAC/Top-IN-1 (5 and 10 mg/kg; PO; daily, for 14 days) exhibits potent oral antitumor activity[1].
| Animal Model: | Female BALB/C nude mice (5-6 weeks, 18-20 g; injected with human K562 cells)[1] | | Dosage: | 5 and 10 mg/kg | | Administration: | PO; daily, for 14 days | | Result: | Exhibited potent oral antitumor activity at 5 mg/kg with a TGI value of 41.4% and a T/C value of 54.3%, and achieved better tumor growth inhibition with a TGI of 68.5% and a T/C of 25.5%. |
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| 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. |
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