Zharp2-1 is an oral effective RIPK2 inhibitor, highly associated with inflammatory bowel disease (IBD). Zharp2-1 blocker muramyl dipeptide (MDP) induces growth of mononuclear cells and induces inflammatory cell factor infection. Zharp2-1 attenuates MDP-induced small inguinal peritonitis, or ameliorates by DNBS-induced large inguinal conjunctivitis.
Zharp2-1 pretreats THP-1 and iBMDM cells for 2 h, and inhibits the release of IL-6 and TNF-α induced by 10 μg/mL MDP or 1 μg/mL L18-MDP for 12 h[1].
Zharp2-1 significantly inhibits MDP-induced cytokine release in PBMCs, with an IC50 of 0.8 nM for IL-8, 8.7 nM for IL-6 and 11.9 nM for TNF-α[1].
Zharp2-1 (15 mg/kg; gavage; once daily for 6 days) protects rats from DNBS-induced colon shortening and colon weight gain, protects rats against DNBS-induced diarrhea. Zharp2-1 significantly ameliorates colonic mucosal structural disruption, muscle thickening and inflammatory infiltration[1].
Pharmacokinetic Analysis[1]
| Route | Dose (mg/kg) | T1/2 (h) | Tmax (h) | Cmax (ng·h/mL) | AUC (ng·h/mL) | Vd (L/kg) | Cl (mL/kg/min) | F (%) | |
| Mouse | iv | 2 | 1.2 | 2989 | 1.1 | 11.1 | |||
| po | 10 | 0.5 | 9610 | 19,236 | 129 | ||||
| Rat | iv | 2 | 1.7 | 7889 | 0.6 | 4.2 | |||
| po | 10 | 3.3 | 3323 | 18,803 | 48 | ||||
| Dog | iv | 1 | 2.1 | 1645 | 1.7 | 9.5 | |||
| po | 5 | 0.7 | 2192 | 10,800 | 131 |