ChEMBL ligand: CHEMBL370962
phosphodiesterase 10A/cAMP and cAMP-inhibited cGMP 3`,5`-cyclic phosphodiesterase 10A in Human [ChEMBL: CHEMBL4409] [GtoPdb: 1310] [UniProtKB: Q9Y233] There should be some charts here, you may need to enable JavaScript!
phosphodiesterase 2A/cGMP-dependent 3`,5`-cyclic phosphodiesterase in Human [ChEMBL: CHEMBL2652] [GtoPdb: 1297] [UniProtKB: O00408] There should be some charts here, you may need to enable JavaScript!

DB	Assay description	Assay Type	Standard value	Standard parameter	Original value	Original units	Original parameter	Reference
phosphodiesterase 10A/cAMP and cAMP-inhibited cGMP 3`,5`-cyclic phosphodiesterase 10A in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4409] [GtoPdb: 1310] [UniProtKB: Q9Y233]
ChEMBL	Proximity Ligation Assay: Isolated cardiomyocytes were washed twice in PBS at room temperature, transferred to 4% paraformaldehyde (PFA) and gently shaken for 30 min, then washed twice again in PBS. The cardiomyocyte suspension was next transferred to 0.8 cm2 wells, each coated with 8 μg laminin (Invitrogen), and incubated at 37° C. for 2 h. PBS was replaced by 0.1% Triton X100 in PBS, and incubated for 10 min at 37° C. Proximity ligation assay was then performed with the Duolink II proprietary system (Olink Bioscience, Uppsala, Sweden), according to the manufacturer's protocol (Soderberg, O., et al., Direct observation of individual endogenous protein complexes in situ by proximity ligation. Nat Methods, 2006. 3(12): 995-1000).Cardiomyocytes were scanned on a Zeiss LSM 710 confocal microscope (excitation 543 nm HeNe laser, through a MBS 488/543 dichroic mirror, emission collected at 565-589 nm). ImageJ 1.44p software (http://imagej.nih.gov/ij) was used for analysis of single-cell intracellular fluorescence intensity by measuring whole cell mean gray value. Results were corrected for background fluorescence signal.	B	7.3	pIC50	>50	nM	IC50	US-11419874-B2. Treatment of tachycardia (2022)
phosphodiesterase 2A/cGMP-dependent 3`,5`-cyclic phosphodiesterase in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2652] [GtoPdb: 1297] [UniProtKB: O00408]
ChEMBL	Inhibition of PDE2A (unknown origin)	B	8.08	pIC50	8.4	nM	IC50	Eur J Med Chem (2024) 271: 116386-116386 [PMID:38614063]
ChEMBL	Inhibition of PDE2 (unknown origin) using [3H]cAMP or [3H]cGMP as substrate measured after 30 mins by liquid scintillation counting method	B	8.32	pIC50	4.8	nM	IC50	Bioorg Med Chem Lett (2019) 29: 481-486 [PMID:30554955]
ChEMBL	Inhibition of PDE2A (unknown origin)	B	8.33	pIC50	4.7	nM	IC50	J Med Chem (2017) 60: 5673-5698 [PMID:28574706]
ChEMBL	Inhibition of human phosphodiesterase 2	B	8.33	pIC50	4.7	nM	IC50	J Med Chem (2005) 48: 3449-3462 [PMID:15887951]
ChEMBL	Inhibition of cGMP stimulated human PDE2A	B	8.33	pIC50	4.7	nM	IC50	Medchemcomm (2015) 6: 2063-2080
ChEMBL	Inhibition of PDE2A (unknown origin) using [3H]cGMP as substrate after 30 mins by scintillation proximity assay	B	8.33	pIC50	4.7	nM	IC50	J Med Chem (2017) 60: 7677-7702 [PMID:28796496]
ChEMBL	Inhibition of PDE2 (unknown origin) using [3H]cAMP as substrate measured after 30 mins by scintillation proximity assay	B	8.33	pIC50	4.7	nM	IC50	Bioorg Med Chem Lett (2019) 29: 481-486 [PMID:30554955]
ChEMBL	Inhibition of human His-tagged PDE2A catalytic domain (578 to 919 residues) expressed in Escherichia coli BL21-CodonPlus(DE3) cells using cGMP as substrate by HTRF assay	B	8.33	pIC50	4.7	nM	IC50	J Med Chem (2016) 59: 7029-7065 [PMID:26908025]
ChEMBL	Proximity Ligation Assay: Isolated cardiomyocytes were washed twice in PBS at room temperature, transferred to 4% paraformaldehyde (PFA) and gently shaken for 30 min, then washed twice again in PBS. The cardiomyocyte suspension was next transferred to 0.8 cm2 wells, each coated with 8 μg laminin (Invitrogen), and incubated at 37° C. for 2 h. PBS was replaced by 0.1% Triton X100 in PBS, and incubated for 10 min at 37° C. Proximity ligation assay was then performed with the Duolink II proprietary system (Olink Bioscience, Uppsala, Sweden), according to the manufacturer's protocol (Soderberg, O., et al., Direct observation of individual endogenous protein complexes in situ by proximity ligation. Nat Methods, 2006. 3(12): 995-1000).Cardiomyocytes were scanned on a Zeiss LSM 710 confocal microscope (excitation 543 nm HeNe laser, through a MBS 488/543 dichroic mirror, emission collected at 565-589 nm). ImageJ 1.44p software (http://imagej.nih.gov/ij) was used for analysis of single-cell intracellular fluorescence intensity by measuring whole cell mean gray value. Results were corrected for background fluorescence signal.	B	8.33	pIC50	4.7	nM	IC50	US-11419874-B2. Treatment of tachycardia (2022)
ChEMBL	Inhibition of PDE2a (unknown origin) using cAMP as substrate after 30 mins by Scintillation proximity assay	B	8.7	pIC50	2	nM	IC50	J Med Chem (2017) 60: 2037-2051 [PMID:28165743]
GtoPdb	-	-	8.8	pIC50	1.58	nM	IC50	Neuropharmacology (2004) 47: 1081-92 [PMID:15555642]
ChEMBL	Measurement of PDE2 Inhibition In Vitro: r-hPDE2A (Accession No. NM_002599, Homo sapiens phosphodiesterase 2A, cGMP-stimulated, transcript variant 1) A mammalian expression cloning vector with recombinant cDNA copy of the gene is purchased from Origene. Protein is expressed via transient transfection of HEK293 cells. The cells are harvested at 48 hours after transfection, washed once with TBS buffer (50 mM Tris-HCl, pH 7.5, 150 mM NaCl), then lysed by sonication in cold homogenization buffer (50 mM Tris-HCl, pH 7.5, 5 mM MgCl2, 1× protease inhibitor cocktail). The homogenate is centrifuged for 30 min at 15,000 g at 4° C. to obtain the soluble cytosolic fraction. The protein concentration of the cytosol is determined using BCA Protein Assay Kit (Pierce) with bovine serum albumin as a standard.Assay:PDE2A is assayed with FL-cAMP as substrate. An enzyme titration is first performed to determine the working concentration of PDE. The concentration of the enzyme giving activity of 100 ΔmP in the absence of inhibitor is deemed an appropriate working concentration for PDE.PDE enzyme is diluted in a standard reaction buffer buffer (10 mM Tris-HCl pH 7.2, 10 mM MgCl2, 0.1% BSA, 0.05% NaN3) according to the titration curve. For PDE2 assay the reaction buffer is supplemented with 1 μM cGMP to fully activate the enzyme. 99 μl of diluted enzyme solution is added into each well in a flat bottom 96-well polystyrene plate and then ˜1 μl of test compound dissolved in 100% DMSO is added. The compounds are mixed and pre-incubated with the enzyme for 10 min at room temperature.The FL-cNMP conversion reaction is initiated by addition of substrate (45 nM final). Enzyme and inhibitor mix (16 μl) and substrate solution (4 μl of 0.225 μM) are combined in a 384-well microtiter plate. The reaction is incubated in the dark at room temperature for 15 min. The reaction is halted by addition of 60 μl of binding reagent (1:400 dilution of IMAP beads in binding buffer supplemented with 1:1800 dilution of antifoam) to each well of the 384-well plate. The plate is incubated at room temperature for 1 hour to allow IMAP binding to proceed to completion, and then placed in an Envision multimode microplate reader (PerkinElmer, Shelton, Conn.) to measure the fluorescence polarization (Δmp).A decrease in cAMP concentration, measured as decreased Δmp, is indicative of inhibition of PDE activity. IC50 values are determined by measuring enzyme activity in the presence of 8 to 16 concentrations of compound ranging from 0.00037 nM to 80,000 nM and then plotting drug concentration versus ΔmP Test well values are normalized to control reactions run on the same plate (values converted to % of control). IC50 values are estimated using nonlinear regression software, fitting a four-parameter one-site dose-response model (XLFit; IDBS, Cambridge, Mass.). Bottom of curve is fixed at 0% of control.	B	9	pIC50	1	nM	IC50	US-10543194-B2. Organic compounds (2020)
ChEMBL	PDE2 Inhibition In Vitro Assay: Assay: PDE2A is assayed with FL-cAMP as substrate. An enzyme titration is first performed to determine the working concentration of PDE. The concentration of the enzyme giving activity of 100 ΔmP in the absence of inhibitor is deemed an appropriate working concentration for PDE.PDE enzyme is diluted in a standard reaction buffer (10 mM Tris-HCl pH 7.2, 10 mM MgCl2, 0.1% BSA, 0.05% NaN3) according to the titration curve. For PDE2 assay the reaction buffer is supplemented with 1 μM cGMP to fully activate the enzyme. 99 μl of diluted enzyme solution is added into each well in a flat bottom 96-well polystyrene plate and then 1 μl of test compound dissolved in 100% DMSO is added. The compounds are mixed and pre-incubated with the enzyme for 10 min at room temperature.	B	9	pIC50	1	nM	IC50	US-10105349-B2. Organic compounds (2018)
ChEMBL	Inhibition of PDE2A (unknown origin)	B	9.07	pIC50	0.86	nM	IC50	J Med Chem (2017) 60: 7658-7676 [PMID:28759228]
ChEMBL	Inhibition of full length recombinant human FLAG-tagged PDE2A3 expressed in sf21 cells using [3H]cGMP as substrate by scintillation proximity assay	B	9.3	pIC50	0.5	nM	IC50	J Med Chem (2017) 60: 5673-5698 [PMID:28574706]
ChEMBL	Inhibition of human PDE2A1 using 3',5'-[3H]cGMP as substrate after 30 mins by scintillation proximity assay	B	10.52	pIC50	0.03	nM	IC50	J Med Chem (2018) 61: 3626-3640 [PMID:29601185]

ChEMBL data shown on this page come from version 36:

Zdrazil B, Felix E, Hunter F, Manners EJ, Blackshaw J, Corbett S, de Veij M, Ioannidis H, Lopez DM, Mosquera JF, Magarinos MP, Bosc N, Arcila R, Kizilören T, Gaulton A, Bento AP, Adasme MF, Monecke P, Landrum GA, Leach AR. (2024). The ChEMBL Database in 2023: a drug discovery platform spanning multiple bioactivity data types and time periods. Nucleic Acids Res., 52(D1). DOI: 10.1093/nar/gkad1004. [EPMCID:10767899] [PMID:37933841]
Davies M, Nowotka M, Papadatos G, Dedman N, Gaulton A, Atkinson F, Bellis L, Overington JP. (2015) 'ChEMBL web services: streamlining access to drug discovery data and utilities.' Nucleic Acids Res., 43(W1). DOI: 10.1093/nar/gkv352. [EPMCID:25883136]