HDAC6-IN-13 (Compound 35m) 是一种强效、高选择性、具有口服活性的HDAC6抑制剂，其IC50为 0.019 μM。 HDAC6-IN-13 也抑制 HDAC1、HDAC2 和 HDAC3，IC50分别为 1.53、2.06 和 1.03 μM。 HDAC6-IN-13 具有明显的血脑屏障通透性和抗炎活性。
| 生物活性 | HDAC6-IN-13 (Compound 35m) is a potent, highly selective, orally activeHDAC6inhibitor with anIC50of 0.019 μM. HDAC6-IN-13 also inhibitsHDAC1,HDAC2andHDAC3withIC50s of 1.53, 2.06 and 1.03 μM, respectively. HDAC6-IN-13 shows significant BBB permeability and anti-inflammatory activity[1]. |
| IC50& Target[1] | HDAC6 0.019 μM (IC50) | HDAC3 1.03 μM (IC50) | HDAC1 1.53 μM (IC50) | HDAC2 2.06 μM (IC50) |
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体外研究
(In Vitro) | HDAC6-IN-13 (Compound 35m) (0.1-1 μM; 24 h) is highly selective toward HDAC6 versus class I HDACs[1].
HDAC6-IN-13 is a slow-on and slow-off tight-binding HDAC6 inhibitor, while exhibits fast-on properties for HDAC1, 2, and 3[1].
HDAC6-IN-13 (5-20 μM; 8 h) shows anti-inflammatory activity in vitro[1].
Western Blot Analysis[1] | Cell Line: | MV4–11 and J774A.1 | | Concentration: | 0.1, 0.2, 0.5 and 1 μM | | Incubation Time: | 24 h | | Result: | Concentration-related accumulation of acetylated tubulin (Ac-Tubulin) was observed, while upregulation of acetylated histone H3 (AcHH3) and acetylated histone H4 (AcHH4) was not apparent even at the concentration of 1 μM. |
Western Blot Analysis[1] | Cell Line: | J774A.1 cells | | Concentration: | 5, 10 and 20 μM | | Incubation Time: | 8 h | | Result: | Inhibited the cleavage of pro-caspase 1 to p20 in a dose-dependent manner, inhibited the
interaction between HDAC6 and dynein. |
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体内研究
(In Vivo) | HDAC6-IN-13 (Compound 35m) (20 mg/kg; p.o. and i.p.; once) displays a remarkable inhibition in LPS-induced inflammation in mice[1].
HDAC6-IN-13 (20 mg/kg; p.o.; once) shows very high oral bioavailability (F% = 93.4%) and significant BBB permeability in mice[1].
| Animal Model: | Male C57BL/6 WT mice, LPS-induced endotoxic shock model[1] | | Dosage: | 20 mg/kg | | Administration: | PO and IP, immediately after the LPS injection | | Result: | Significantly decreased the serum IL-1β levels in LPS-induced mice via both ip and po administration. |
| Animal Model: | Male CD-1 mice[1] | | Dosage: | 5 mg/kg or 20 mg/kg | | Administration: | IV (5 mg/kg) or PO (20 mg/kg) (Pharmacokinetic Study) | | Result: | Pharmacokinetics Characterization of HDAC6-IN-13 (Compound 35m) with iv and Oral Administrationa[1]
| PK parameters | HDAC6-IN-13 | HDAC6-IN-13 | | administered dose (mg/kg) | iv at 5 mg/kg | oral at 20 mg/kg | | Cmax(ng/mL) | 4604 ± 551 | 5570 ± 551 | | t1/2(h) | 7.95 ± 0.370 | 6.80 ± 0.145 | | AUC0–inf(ngoh/mL) | 2755 ± 395 | 10292 ± 1385 | | F% | n/a | 93.4 ± 12.6 |
aHDAC6-IN-13 was administrated via iv and po (n = 3). The blood sample was collected at different time points after dosing, and the plasma concentration of HDAC6-IN-13 was determined via LC-MS/MS. The area under the plasma concentration versus time curve (AUC) was calculated using the linear trapezoidal method. The pharmacokinetic parameters were obtained using the noncompartmental method. Data are shown as mean ± SD. |
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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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