Selective mPGES-1 Inhibitor Ameliorated Adjuvant-Induced Arthritis in the Rat Model

Table 1

Preliminary ADMET properties of MPO-0144.

Property	Parameter	Value
Absorption	pKa	2.96
	LogP	6.77
	Solubility	Equilibrium solubility			Kinetic solubility in 5% DMSO
		7.51 ± 1.44 μM (4.08 ± 0.78 μg/mL)			342.9 ± 1.5 μM (186.3 ± 0.8 μg/mL)
	PAMPA^a	LogPe (cm/sec) = −4.19 ± 0.02 (medium)
	P-glycoprotein	2.13% inhibition at 10 μM
Metabolism	CYP450^b	CYP1A2	CYP2C9	CYP2C19		CYP2D6	CYP3A4
		21.5%	51.9%	52.4%		4.1%	47.8%
Toxicity	hERG	7.37 μM
	Ames	TA98/TA100 without S9			TA98/TA100 with S9
		Negative/negative			Negative/negative
	Acute toxicity^c	LD50 => 2,000 mg/kg d

^aParallel artificial membrane permeability assay. ^b%inhibition of isozymes after treatment of MPO-0144 at 10 μM. Positive control for inhibition assay: CYP1A2 (α-naphthoflavone, 91.1% @10 μM), CYP2C9 (sulfaphenazole, 94.3% @10 μM), CYP2C19 (amitriptyline, 88.9% @100 μM), CYP2D6 (quinidine, 95.7% @10 μM), and CYP3A4 (ketoconazole, 96.8% @10 μM). ^cOral rat acute toxicity. ^dALD (approximate lethal dose).