Table 2.

Structural determinants of biological and physical properties of EP2 allosteric potentiators

Compound		EP2potentiation*	IC50 for cyto-toxicity(μM)†	Solub-ility(μM)‡	Nano-particle-diameter(nm)§	Percent of compound- as soluble monomer║
1		4.2 ± 0.6(14)	248(5)	< 25	410 ± 7.9(4)	1.86 ± 0.50(5)
2		3.8 ± 0.9(8)	50(5)	NM	427 ± 15.2(4)	0.83 ± 0.18(3)
3		3.0 ± 0.9(5)	4,420(3)	< 25	634 ± 20.2(4)	7.82 ± 2.75(3)
4		2.2 ± 1.1(6)	107(3)	< 25	591 ± 12.9(4)	1.2
5		0.8 ± 0.1(5)	NM	> 800	UD	96.8 ± 1.24(4)
6		1.8 ± 0.3(6)	1,090(3)	< 25	2,560 ± 477(4)	NM
7		1.2 ± 0.1(5)	NM	< 25	568 ± 32.7(4)	2.05 ± 0.66(3)
8		1.3 ± 0.2(6)	483 (3)	NM	NM	NM
9		1.4 ± 0.1(6)	36(3)	NM	NM	NM
10		1.9 ± 0.5(5)	NM	< 25	625 ± 80.5(4)	NM
11		3.9 ± 0.5(5)	NM	< 25	678 ± 37.6(4)	NM
12		1.7 ± 0.3(5)	NM	< 25	610 ± 67.9(4)	NM
13		2.2 ± 0.3(5)	NM	< 25	676 ± 17.5(4)	NM
Doxorubicin		NM	0.35(3)	NM	UD	NM

NM, not measured; UD, undetectable. Data presented as mean ± SEM (n).

*The fold shift to the left of the PGE₂ EC₅₀ in 20 μM compound.

^†The mean IC₅₀ for toxicity in C6G cells after 48 h incubation, doxorubicin as positive control.

^‡Compound solubility in PBS determined by nephelometry.

^§Diameter of nanoparticle formed by compound (20 μM), estimated by dynamic light scattering (DLS).

^‖% monomer remaining in a 20 μM solution in 0.2% DMSO after centrifugation at 100,000 g for 10 min, determined by LC-MS.