TABLE 3

PDE4 inhibitors tested for their selectivity against different PDE4 isoforms or construct lengths of the same PDE4 subtype

Compound	Study	Construct	Construct Category	Truncation/Modification	IC₅₀
					nM
CDP840	Perry et al., 1998	PDE4B2	Short		1.9
		PDE4B3	Long		3.8
		PDE4D2	Supershort		2.9
		PDE4D3	Long		2.6
Chlorbipram	Zhang et al., 2013	PDE4B2	Short		99,300
		PDE4B5	Supershort		8320
Cilomilast	Wunder et al., 2013	PDE4D3		cat dom	20.5
		PDE4D3	Long		10.1
Denbufylline	Owens et al., 1997a	PDE4A4	Long		295
		PDE4A4	cat dom	UCR1-UCR2 deleted	550
D159153	Wunder et al., 2013	PDE4D3		cat dom	20,500
		PDE4D3	Long		68.3
D159404	Wunder et al., 2013	PDE4D3		cat dom	20,000
		PDE4D3	Long		380
Etazolate	Wunder et al., 2013	PDE4D3		cat dom	143
		PDE4D3	Long		240
GEBR-32a	Ricciarelli et al., 2017	PDE4D1	Short		4970
		PDE4D2	Supershort		2890
		PDE4D3	Long		2420
		PDE4D5	Long		3180
		PDE4D7	Long		1140
	Prosdocimi et al., 2018	PDE4D	cat dom	cat dom, no C-term	2300
		PDE4D3	Long	PKA-mimetic, ERK-ablative	1000
(S)-(+)-GEBR-32a	Cavalloro et al., 2020	PDE4D	cat dom	cat dom, no C-term	19,500
		PDE4D3	Long	PKA-mimetic, ERK-ablative	2100
(R)-(-)-GEBR-32a	Cavalloro et al., 2020	PDE4D	cat dom	cat dom, no C-term	31,800
		PDE4D3	Long	PKA-mimetic, ERK-ablative	15,500
GEBR-7b	Prosdocimi et al., 2018	PDE4D	cat dom	cat dom, no C-term	1600
		PDE4D3	Long	PKA-mimetic, ERK-ablative	1100
GEBR-20b	Prosdocimi et al., 2018	PDE4D	cat dom	cat dom, no C-term	800
		PDE4D3	Long	PKA-mimetic, ERK-ablative	600
GEBR-4a	Prosdocimi et al., 2018	PDE4D	cat dom	cat dom, no C-term	7000
		PDE4D3	Long	PKA-mimetic, ERK-ablative	2100
GEBR-11b	Prosdocimi et al., 2018	PDE4D	cat dom	cat dom, no C-term	900
		PDE4D3	Long	PKA-mimetic, ERK-ablative	400
GEBR-26g	Prosdocimi et al., 2018	PDE4D	cat dom	cat dom, no C-term	17,000
		PDE4D3	Long	PKA-mimetic, ERK-ablative	3500
GEBR-54	Prosdocimi et al., 2018	PDE4D	cat dom	cat dom, no C-term	20,000
		PDE4D3	Long	PKA-mimetic, ERK-ablative	4600
GEBR-18b	Prosdocimi et al., 2018	PDE4D	cat dom	cat dom, no C-term	16,000
		PDE4D3	Long	PKA-mimetic, ERK-ablative	4800
GEBR-18a	Prosdocimi et al., 2018	PDE4D	cat dom	cat dom, no C-term	23,000
		PDE4D3	Long	PKA-mimetic, ERK-ablative	5000
Lirimilast	Wunder et al., 2013	PDE4D3		cat dom	3725
		PDE4D3	Long		54.3
Oglemilast	Wunder et al., 2013	PDE4D3		cat dom	0.5
		PDE4D3	Long		1.1
Piclamilast	Wunder et al., 2013	PDE4D3		cat dom	0.064
		PDE4D3	Long		0.12
PMNPQ	Wunder et al., 2013	PDE4D3		cat dom	115
		PDE4D3	Long		0.43
Roflumilast	Wunder et al., 2013	PDE4D3		cat dom	0.039
		PDE4D3	Long		0.076
Roflumilast N-oxide	Wunder et al., 2013	PDE4D3		cat dom	0.079
		PDE4D3	Long		0.26
Rolipram	Bruno et al., 2009	PDE4D1	Short		910
		PDE4D2	Supershort		1170
		PDE4D3	Long		550
	Wunder et al., 2013	PDE4D3		cat dom	510
		PDE4D3	Long		72.8
	Zhang et al., 2013	PDE4D4	Long		470
		PDE4D5	Long		190
	Wang et al., 2003	PDE4D6	Supershort		57
		PDE4D7	Long		42
R-rolipram	Perry et al., 1998	PDE4B2	Short		60.5
		PDE4B3	Long		69
		PDE4D2	Supershort		26.9
		PDE4D3	Long		84.3
Ro20-1724	Owens et al., 1997a	PDE4A4	Long		1450
		PDE4A4	cat dom	UCR1-UCR2 deleted	4154
YM976	Wunder et al., 2013	PDE4D3		cat dom	0.34
		PDE4D3	Long		0.73
Zardaverine	Wunder et al., 2013	PDE4D3		cat dom	163
		PDE4D3	Long		65.3
4a	Bruno et al., 2009	PDE4D1	Short		7090
		PDE4D2	Supershort		9180
		PDE4D3	Long		2860
4e	Liang et al., 2020	PDE4B2	Short	cat dom	10
		PDE4B1	Long		8
		PDE4D2	Supershort	cat dom	17
		PDE4D7	Long		9

cat dom, catalytic domain; C-term, C terminus.