| Hazard Information | Back Directory | [Uses]
sEH/HDAC6-IN-1 (compound M9) is a selective, orally active dual inhibitor for sEH and HDAC6, with IC50s of 2 nM, 0.72 nM and 5 nM, for human sEH, murine sEH and HDAC6, respectively. sEH/HDAC6-IN-1 reveals analgesic and anti-inflammatory effects[1]. | [in vivo]
sEH/HDAC6-IN-1 reveals a plasma protein binding (PBB) percentage of 81.40% in SD rats[1].
sEH/HDAC6-IN-1 (p.o., 100 mg/kg, 7 days) reveals analgesic effects in SNI mice[1].
sEH/HDAC6-IN-1 (5 mg/kg, i.p., 4-12 h) inhibits LPS induced inflammation and the release of IL-6, TNF-α and MCP-5 in C57BL/6 mice[1].
sEH/HDAC6-IN-1 (i.v.:10 mg/kg, p.o.:100 mg/kg) reveals a pharmacokinetics profils in SD rats[1]:
Pharmacokinetic Analysis of sEH/HDAC6-IN-1 in SD rats[1]
| route | Dose (mg/kg) | Tmax (h) | Cmax (μM) | T1/2 (h) | CL (L/h/kg) | VZ (L/kg) | AUC0-8 (μM·h) | AUC0-∞ (μM·h) | F (%) | | iv | 10 | 0.03 | 261.20 | 1.58 | 0.21 | 0.43 | 36.76 | 38.10 | 10.82 | | po | 100 | 0.50 | 13.09 | 1.31 | 1.80 | 3.43 | 19.89 | 22.85 | - |
| Animal Model: | alleviating spared nerve injury (SNI)-induced neuropathic pain in C57BL/6 mice[1] | | Dosage: | 100 mg/kg | | Administration: | oral administration for 7 days | | Result: | decreased PWT values. |
| Animal Model: | LPS induced acute inflammation in C57BL/6 mice[1] | | Dosage: | 5 mg/kg | | Administration: | i.p., 4-12 h | | Result: | Survived 66.7% mice at 28 h, 44.44% mice at 35 h, 22.22% mice at 72 h. |
| [IC 50]
murine sEH: 0.72 nM (IC50); human sEH: 2 nM (IC50); HDAC6: 5 nM (IC50); HDAC1: 0.2731 μM (IC50); HDAC2: 0.8 μM (IC50); HDAC3: 0.49 μM (IC50); HDAC11: 0.3142 μM (IC50) | [References]
[1] Chen Y,et al., Design and Synthesis of Dual-Targeting Inhibitors of sEH and HDAC6 for the Treatment of Neuropathic Pain and Lipopolysaccharide-Induced Mortality. J Med Chem. 2024 Feb 8;67(3):2095-2117. DOI:10.1021/acs.jmedchem.3c02006 |
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