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Apoptosis" style="display: inline; color: #c13a36">凋亡 (Apoptosis)，能将细胞阻滞在 S 期。

HDAC/Top-IN-1 is an orally active and pan HDAC/Top dual inhibitor with IC 50 s of 0.036 μM, 0.14 μM, 0.059 μM, 0.089 μM and 9.8 μM for HDAC1, HDAC2, HDAC3, HDAC6 and HDAC8. HDAC/Top-IN-1 efficiently induces apoptosis with S cell-cycle arrest in HEL cells. HDAC/Top-IN-1 has exhibits excellent in vivo antitumor efficacy [1].

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 IC 50 s 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.

HDAC/Top-IN-1 exhibits good metabolic properties with a half-life (T 1/2 ) 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%.

2411379-14-9

C29H25FN4O4

512.53

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years