Table 1 Synergy scores for adenosine... | American Society of Hematology

Table 1

Synergy scores for adenosine receptor/PDE inhibitor combinations

PDE inhibitor and selectivity		Adenosine receptor agonist and selectivity
		A1 > A3 ≫ A2A = A2B	A1 = A2A = A3 > A2B	A2A > A3 > A1 ≫ A2B	A3 > A1 > A2A ≫ A2B	A3 > A1 > A2A ≫ A2B
		(S)-ENBA	HE-NECA	CGS-21680	Chloro-IB-MECA	IB-MECA
pan	IBMX	0.09	0.27	0.38	0.34	0.11
pan	Pentoxifylline	0.50	0.28	0.23	0.06	0.09
pan	Dipyridamole	0.17	0.08	0.10	0.20	0.07
1	Vinpocetine	0.26	0.27	0.29	0.13	0.21
2	BAY 60-7550	2.82*	3.56*	3.84*	2.09*	1.80*
2,3,4	Trequinsin	4.53*	10.34*	6.96*	5.91*	6.38*
3	Cilostamide	1.15*	1.88*	0.88	1.10*	1.46*
3	Cilostazol	1.61*	4.07*	4.08*	1.30*	1.55*
3	Siguazodan	0.40	0.73	1.44*	0.42	0.61
3	Milrinone	1.31*	0.33	0.70	0.26	0.40
3,4	Zardaverine	3.25*	4.40*	5.12*	3.82*	4.90*
4	R-(-)-Rolipram	1.89*	4.38*	1.93*	1.65*	2.69*
4	RO-20-1724	0.74	3.52*	0.90	1.60*	1.82*
4	Roflumilast	2.19*	3.24*	4.39*	2.85*	3.21*
3,4,10,11	Ibudilast	0.67	0.98	2.21*	0.74	1.16*
1,5,6,10,11	Zaprinast	0.13	0.09	0.05	0.07	0.03
1,5,6	Sildenafil	0	0	0.07	0	0
5	Vardenafil	0	0	0	0	0
6,7,10	Papaverine	1.95*	2.07*	0.95	2.32*	1.68*
7	BRL-50481	1.23*	1.41*	1.98*	1.89*	1.51*

PDE inhibitor and selectivity		Adenosine receptor agonist and selectivity
		A1 > A3 ≫ A2A = A2B	A1 = A2A = A3 > A2B	A2A > A3 > A1 ≫ A2B	A3 > A1 > A2A ≫ A2B	A3 > A1 > A2A ≫ A2B
		(S)-ENBA	HE-NECA	CGS-21680	Chloro-IB-MECA	IB-MECA
pan	IBMX	0.09	0.27	0.38	0.34	0.11
pan	Pentoxifylline	0.50	0.28	0.23	0.06	0.09
pan	Dipyridamole	0.17	0.08	0.10	0.20	0.07
1	Vinpocetine	0.26	0.27	0.29	0.13	0.21
2	BAY 60-7550	2.82*	3.56*	3.84*	2.09*	1.80*
2,3,4	Trequinsin	4.53*	10.34*	6.96*	5.91*	6.38*
3	Cilostamide	1.15*	1.88*	0.88	1.10*	1.46*
3	Cilostazol	1.61*	4.07*	4.08*	1.30*	1.55*
3	Siguazodan	0.40	0.73	1.44*	0.42	0.61
3	Milrinone	1.31*	0.33	0.70	0.26	0.40
3,4	Zardaverine	3.25*	4.40*	5.12*	3.82*	4.90*
4	R-(-)-Rolipram	1.89*	4.38*	1.93*	1.65*	2.69*
4	RO-20-1724	0.74	3.52*	0.90	1.60*	1.82*
4	Roflumilast	2.19*	3.24*	4.39*	2.85*	3.21*
3,4,10,11	Ibudilast	0.67	0.98	2.21*	0.74	1.16*
1,5,6,10,11	Zaprinast	0.13	0.09	0.05	0.07	0.03
1,5,6	Sildenafil	0	0	0.07	0	0
5	Vardenafil	0	0	0	0	0
6,7,10	Papaverine	1.95*	2.07*	0.95	2.32*	1.68*
7	BRL-50481	1.23*	1.41*	1.98*	1.89*	1.51*

MM.1S cells were incubated with adenosine receptor agonists and PDE inhibitors alone and in combination in multiple doses and ratios in a 6 × 6 dose matrix (as described in Figure 1). The synergy scores were determined as detailed in the legend for Figure 1. The activity of 5 adenosine receptor agonists and 20 PDE inhibitors was examined. The selectivity of each of these agents is shown. All of the adenosine receptor agonists target the A2A receptor but differ in potency, with selectivity being concentration dependent.²⁰ PDE inhibitor specificity is as described.^19,21

PDE indicates phosphodiesterase; and IBMX, 3-isobutyl-1-methylxanthine.

Adenosine receptor agonist/PDE inhibitors combinations with synergy scores > 1.

View Large

This Feature Is Available To Subscribers Only