Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK3SHT2)

• DOT Name: 3',5'-cyclic-AMP phosphodiesterase 7B (PDE7B)
• Synonyms: EC 3.1.4.53; cAMP-specific phosphodiesterase 7B
• Gene Name: PDE7B
• UniProt ID: PDE7B_HUMAN
• EC Number: 3.1.4.53
• Pfam ID: PF00233
• Sequence:
  MSCLMVERCGEILFENPDQNAKCVCMLGDIRLRGQTGVRAERRGSYPFIDFRLLNSTTYS
  GEIGTKKKVKRLLSFQRYFHASRLLRGIIPQAPLHLLDEDYLGQARHMLSKVGMWDFDIF
  LFDRLTNGNSLVTLLCHLFNTHGLIHHFKLDMVTLHRFLVMVQEDYHSQNPYHNAVHAAD
  VTQAMHCYLKEPKLASFLTPLDIMLGLLAAAAHDVDHPGVNQPFLIKTNHHLANLYQNMS
  VLENHHWRSTIGMLRESRLLAHLPKEMTQDIEQQLGSLILATDINRQNEFLTRLKAHLHN
  KDLRLEDAQDRHFMLQIALKCADICNPCRIWEMSKQWSERVCEEFYRQGELEQKFELEIS
  PLCNQQKDSIPSIQIGFMSYIVEPLFREWAHFTGNSTLSENMLGHLAHNKAQWKSLLPRQ
  HRSRGSSGSGPDHDHAGQGTESEEQEGDSP
• Function: Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in the control of cAMP-mediated neural activity and cAMP metabolism in the brain.
• Tissue Specificity: Highly expressed in brain . Also expressed in heart, liver, skeletal muscle and pancreas .
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Metabolic pathways (hsa01100)
  Morphine addiction (hsa05032)
• Reactome Pathway: G alpha (s) signalling events (R-HSA-418555)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Biotransformations of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Testosterone enanthate	DMB6871	Approved	3',5'-cyclic-AMP phosphodiesterase 7B (PDE7B) increases the hydrolysis of Testosterone enanthate.	[15]
[3H]cAMP	DMZRQU7	Investigative	3',5'-cyclic-AMP phosphodiesterase 7B (PDE7B) increases the hydrolysis of [3H]cAMP.	[16]

13 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of 3',5'-cyclic-AMP phosphodiesterase 7B (PDE7B).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 3',5'-cyclic-AMP phosphodiesterase 7B (PDE7B).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of 3',5'-cyclic-AMP phosphodiesterase 7B (PDE7B).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of 3',5'-cyclic-AMP phosphodiesterase 7B (PDE7B).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of 3',5'-cyclic-AMP phosphodiesterase 7B (PDE7B).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of 3',5'-cyclic-AMP phosphodiesterase 7B (PDE7B).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of 3',5'-cyclic-AMP phosphodiesterase 7B (PDE7B).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of 3',5'-cyclic-AMP phosphodiesterase 7B (PDE7B).	[9]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of 3',5'-cyclic-AMP phosphodiesterase 7B (PDE7B).	[10]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of 3',5'-cyclic-AMP phosphodiesterase 7B (PDE7B).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of 3',5'-cyclic-AMP phosphodiesterase 7B (PDE7B).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of 3',5'-cyclic-AMP phosphodiesterase 7B (PDE7B).	[11]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of 3',5'-cyclic-AMP phosphodiesterase 7B (PDE7B).	[14]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of 3',5'-cyclic-AMP phosphodiesterase 7B (PDE7B).	[6]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of 3',5'-cyclic-AMP phosphodiesterase 7B (PDE7B).	[13]

References

• [1] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [2] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Bisphenol A effects on gene expression in adipocytes from children: association with metabolic disorders. J Mol Endocrinol. 2015 Jun;54(3):289-303.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [8] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [9] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [10] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [15] Bioavailability of testosterone enanthate dependent on genetic variation in the phosphodiesterase 7B but not on the uridine 5'-diphospho-glucuronosyltransferase (UGT2B17) gene. Pharmacogenet Genomics. 2011 Jun;21(6):325-32. doi: 10.1097/FPC.0b013e328344c5c6.
• [16] Identification of human PDE7B, a cAMP-specific phosphodiesterase. Biochem Biophys Res Commun. 2000 May 19;271(3):575-83.