Zharp2-1

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