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Apoptosis" style="display: inline; color: #c13a36">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。

Tubulin/HDAC-IN-1 is a dual tubulin and HDAC-IN-1 inhibitor through CH/π interaction with tubulin and hydrogen bond interaction with HDAC8. Tubulin/HDAC-IN-1 inhibits tubulin polymerization and selectively inhibits HDAC8 ( IC 50 : 150 nM). Tubulin/HDAC-IN-1 has cytotoxicity against various human cancer cells, also arrests cell cycle in the G2/M phase and induces cell apoptosis. Tubulin/HDAC-IN-1 can be used in the research of hematologic and solid tumors such as neuroblastoma, leukemia [1].

Tubulin/HDAC-IN-1 (Compound 12a, 72 h) shows cytotoxicity against various human cancer cell lines with an averaged IC 50 value 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 (IC 50 : 150 nM), inhibits HDAC6 and HDAC11 with IC 50 values 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 good in vitro metabolic 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 t 1/2 (h) CL int t 1/2 CL int 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 (IC 50 nM): 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.

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.

2413587-26-3

C21H18N4O3

374.39

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