NN-390 是一种有效的选择性HDAC6抑制剂，其IC50为 9.8 nM。NN-390 可穿透血脑屏障。NN-390 在转移性第 3 组成神经管细胞瘤中显示出研究潜力。
| 生物活性 | NN-390 is a potent and selectiveHDAC6inhibitor, with anIC50of 9.8 nM. NN-390 penetrates the blood-brain barrier (BBB). NN-390 shows study potential in metastatic Group 3 MB (medulloblastoma)[1]. |
| IC50& TargetHDAC | HDAC2 >5 μM (IC50) | HDAC1 >5 μM (IC50) | HDAC6 9.8 nM (IC50) | HDAC3 >1 μM (IC50) | HDAC8 >1 μM (IC50) | HDAC11 >1 μM (IC50) |
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体外研究
(In Vitro) | NN-390 exhibits cellular potency withIC50values of 1.19 μM in MV4-11 cells and 1.38 μM in MM.1S cells while having minimal effects on noncancerous counterparts (IC50>50 μM in MRC-9)[1].
NN-390 (72 h) strongly decreases proliferation in HD-MB03 cells, with anIC50of 0.13 μM, and significantly impairs self-renewal of BTIC-enriched HD-MB03s[1].
NN-390 (0-2 μM, 1 h) markedly increases acetylation of α-tubulin and minimally changes acetylated histone H3[1].
NN-390 (6 h) results in acetylation of α-tubulin from concentrations as low as 0.1 μM (0-0.2 μM), and dose-dependent increases in acetylation of α-tubulin (0-0.2 μM)[1].
NN-390 (0-2 μM, 24 h) promotes cancer cells apoptosis in MV4-11 cells[1].
Immunofluorescence | Cell Line: | HeLa cells[1] | | Concentration: | 0, 0.1, 0.25, 1, 2 μM | | Incubation Time: | 1 h | | Result: | Markedly increased acetylation of α-tubulin and minimally changed acetylated histone H3. |
Western Blot Analysis | Cell Line: | AML (MV4-11) cells[1] | | Concentration: | 0, 0.1, 0.5, 1, 5 μM | | Incubation Time: | 6 h | | Result: | Resulted in acetylation of α-tubulin from concentrations as low as 0.1 μM and with limited acetylation of histone H3 at only the highest concentration of 5 μM. |
Western Blot Analysis | Cell Line: | Group 3 MB (HD-MB03) cells[1] | | Concentration: | 0, 0.053, 0.106, 0.158, 0.211 μM | | Incubation Time: | 6 h | | Result: | Dose-dependent increased in acetylation of α-tubulin from the lowest concentration of 53 nM, with no observable change in acetylation of off-target histone H3 up to 211 nM. |
Apoptosis Analysis | Cell Line: | MV4-11 cells[1] | | Concentration: | 0, 0.25, 0.75, 1, 2 μM | | Incubation Time: | 24 h | | Result: | Promoted cancer cells apoptosis, 39% of cancer cells were undergoing late-stage apoptosis after 18 h at 2 μM, and 11% of cells were in the late apoptosis stage at 0.25 μM. |
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体内研究
(In Vivo) | NN-390 (male CD-1 mice, 20 mg/kg, IP, single dose) increases plasma stability[1].
NN-390 can improve PAMPA (parallel artificial membrane permeability assay)-BBB (blood-brain barrier) score[1].
Pharmacokinetic Parameters of NN-390 in male male CD-1 mice[1].
| Compound | KT-531 | 5a; NN-390 | | t1/2(h) | 1.05 | 1.90 | | Cmax(ng/mL) | 493 | 750 | | AUClast(h*ng/mL) | 1576 | 2523 | | AUClnf(h*ng/mL) | 1519 | 2548 | | AUC/D (h*ng/mL) | 79 | 126 |
| Animal Model: | CD-1 mice (male, n=3)[1] | | Dosage: | 20 mg/kg | | Administration: | IP, single dose (Pharmacokinetic Analysis) | | Result: | Had a half-life of 115 min in human plasma, a 2.8-fold increase in stability. |
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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. |
