TABLE 4

PDE4 inhibitors tested for their selectivity against different PDE4 conformational states or PDE4 isoforms in different cellular fractions

Compound	Study	Construct	Construct Category	Mutation/Modification/Cellular Fraction	IC₅₀
					nM
A-33	Fox et al., 2014	PDE4B1	Long	PKA-mimetic, ERK-ablative	32
		PDE4B1	Long	L674Q, PKA-mimetic, ERK-ablative	2035
		PDE4D7	Long	PKA-mimetic, ERK-ablative	1569
		PDE4D7	Long	Q594L, PKA-mimetic, ERK-ablative	21
BPN14770	Zhang et al., 2018	PDE4D7	Long	—	1018
		PDE4D7	Long	PKA-mimetic, ERK-ablative	7.8
		PDE4D3	Long	PKA-mimetic, ERK-ablative	7.4
		PDE4D2	Supershort	ERK-ablative	127
		PDE4B1	Long	PKA-mimetic, ERK-ablative	2013
Cilomilast	Wallace et al., 2005	PDE4A11	Long	Cytosolic	34
		PDE4A11	Long	Particulate P2	34
		PDE4A4	Long	Cytosolic	61
		PDE4A4	Long	Particulate P2	59
		PDE4A10	Long	Cytosolic	130
Denbufylline	Wallace et al., 2005	PDE4A11	Long	Cytosolic	250
		PDE4A11	Long	Particulate P2	310
		PDE4A4	Long	Cytosolic	560
		PDE4A4	Long	Particulate P2	460
		PDE4A10	Long	Cytosolic	590
PMNPQ	Burgin et al., 2010	PDE4D7	Long	PKA-mimetic	5
		PDE4D7	Long	PKA-mimetic, Phe196Ala	170
		PDE4D7	Long	PKA-mimetic, Phe201Ala	310
		PDE4D7	Long	PKA-mimetic, ERK-ablative	0.52
		PDE4D2	Supershort	ERK-ablative	0.66
		PDE4B1	Long	PKA-mimetic	4.4
Roflumilast	Wallace et al., 2005	PDE4A11	Long	Cytosolic	4.8
		PDE4A11	Long	Particulate P2	3.9
		PDE4A4	Long	Cytosolic	9.0
		PDE4A4	Long	Particulate P2	2.5
		PDE4A10	Long	Cytosolic	4.1
Rolipram	Zhang et al., 2018	PDE4D7	Long	—	675
		PDE4D7	Long	PKA-mimetic, ERK-ablative	32
		PDE4D3	Long	PKA-mimetic, ERK-ablative	29
		PDE4D2	Supershort	ERK-ablative	142
		PDE4B1	Long	PKA-mimetic, ERK-ablative	175
	Huston et al., 1996	PDE4A4	Long	Particulate	195
		PDE4A4	Long	Cytosolic	1600
	Wallace et al., 2005	PDE4A11	Long	Cytosolic	720
		PDE4A11	Long	Particulate P2	660
		PDE4A4	Long	Cytosolic	1310
		PDE4A4	Long	Particulate P2	260
		PDE4A10	Long	Cytosolic	64
	Rena et al., 2001	PDE4A10	Long	Particulate P1	54
		PDE4A10	Long	Particulate P2	52
		PDE4A10	Long	Cytosolic	56
	Huston et al., 1997	PDE4B1	Long	Particulate P1	100
		PDE4B1	Long	Particulate P2	50
		PDE4B1	Long	Cytosolic	80
		PDE4B3	Long	Particulate P1	140
		PDE4B3	Long	Particulate P2	100
		PDE4B3	Long	Cytosolic	50
		PDE4B2	Short	Particulate P1	180
		PDE4B2	Short	Particulate P2	210
		PDE4B2	Short	Cytosolic	20
	Bolger et al., 1997	PDE4D1	Short	Particulate P2	n/a
		PDE4D1	Short	Cytosolic	50
		PDE4D2	Supershort	Particulate P2	n/a
		PDE4D2	Supershort	Cytosolic	50
		PDE4D3	Long	Particulate P2	320
		PDE4D3	Long	Cytosolic	140
		PDE4D4	Long	Particulate P2	50
		PDE4D4	Long	Cytosolic	60
		PDE4D5	Long	Particulate P2	590
		PDE4D5	Long	Cytosolic	80
Ro 20-1724	Wallace et al., 2005	PDE4A11	Long	Cytosolic	990
		PDE4A11	Long	Particulate P2	910
		PDE4A4	Long	Cytosolic	2930
		PDE4A4	Long	Particulate P2	2900
		PDE4A10	Long	Cytosolic	1240
RS25344	Burgin et al., 2010	PDE4D7	Long	PKA-mimetic	19
		PDE4D7	Long	PKA-mimetic, Phe196Ala	4.1
		PDE4D7	Long	PKA-mimetic, Phe201Ala	6.2
		PDE4D7	Long	PKA-mimetic, ERK-ablative	0.91
		PDE4D2	Supershort	ERK-ablative	0.81
		PDE4B1	Long	PKA-mimetic	9.4
	Alvarez et al., 1996	PDE4D3	Long	—	3.16
		PDE4D3	Long	PKA-mimetic	0.5
RS33793	Alvarez et al., 1996	PDE4D3	Long	—	39.8
		PDE4D3	Long	PKA-mimetic	0.2

n/a, not applicable.