Table 10.

Comparison of the RARα Agonist Potency, selectivity versus the RARβ and RARγ Human and Mouse Receptors, Human Intrinsic Clearance and Pharmacokinetic Profile in Rat for 56 and 15.

Binding Activity		Agonist Potency and Selectivity			PK
Compd	RARα rel IC50a	RARα rel EC50 bm/chu	β/α ratio bm/chu	γ/α ratio bm/chu	intrinsic Clintd	rat poe			f Log D pH 7.4
					human	AUC	Cl	F%
56	3.6	1.6/0.6	200/298	11,000/>13,000	5.3	70,765	7	40	1.8
15	115	10.4/8.1	33/289	452/2322	26	1674	2	0.3	2.8
AM 580(2)	9	0.02/0.13	1130/162	826/505	15.6	–	–	–	2.8

^aRARα binding assay. The relative IC₅₀ is the mean IC₅₀ for each compound divided by the mean IC₅₀ of ATRA (IC₅₀ = 0.6 nM). Values were obtained from three separate experiments.

^bm = mouse receptor, see Table 1.

^chu = human receptor, see Table 9.

^dHuman microsomes Cl_int (µL/min/mg protein).

^eAUC po ng·min mL⁻¹,Cl mL/kg/min.

^fLog D see Table 2.