Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMJPE61)

• Drug Name: PF-02545920 Drug Info
• Synonyms: 1037309-45-7; 2-((4-(1-Methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)quinoline succinate; UNII-TJ5KAZ8T5G; TJ5KAZ8T5G; PF-2545920 succinate; SCHEMBL439127; CTK8C0559; DTXSID90647726; ANW-64894; AKOS016005150; KB-80291; Quinoline, 2-((4-(1-methyl-4-(4-pyridinyl)-1H-pyrazol-3-yl)phenoxy)methyl)-, butanedioate (1:1); AX8234870; TC-153639; Quinoline,2-[[4-[1-methyl-4-(4-pyridinyl)-1H-pyrazol-3-yl]phenoxy]methyl]-,succinate salt; 2-[[4-[1-Methyl-4-(4-pyridyl)pyrazol-3-yl]phenoxy]methyl]quinoline

Indication

Disease Entry	ICD 11	Status	REF
Huntington disease	8A01.10	Phase 2	[1]
Schizophrenia	6A20	Phase 2	[2]

• Cross-matching ID:
  PubChem CID: 11581936
  CAS Number: CAS 898562-94-2
  TTD Drug ID: DMJPE61

Molecule-Related Drug Atlas

Drug(s) Targeting Phosphodiesterase 10A (PDE10)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tofisopam	DMTGNWU	Hyperuricaemia	5C55.Y	Phase 2	[4]
TAK-063	DMP1873	Schizophrenia	6A20	Phase 2	[5]
OMS824	DMA4OGL	Huntington disease	8A01.10	Phase 2	[6]
Lu AF11167	DMJOYNZ	Schizophrenia	6A20	Phase 2	[7]
FRM-6308	DMNCOE1	Schizophrenia	6A20	Phase 1b	[8]
PBF-999	DMBSQH9	Huntington disease	8A01.10	Phase 1	[9]
RG7203	DMYX4NP	Schizophrenia	6A20	Phase 1	[10]
AMG 579	DMRMC7U	Schizophrenia	6A20	Phase 1	[11]
Pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine derivative 1	DMC8935	N. A.	N. A.	Patented	[12]
Pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine derivative 2	DM4CSBD	N. A.	N. A.	Patented	[12]

Drug(s) Affected By Lipid transferase CIDEA (CIDEA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[13]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[14]
Tolcapone	DM8MNVO	Parkinson disease	8A00.0	Approved	[15]
Menthol	DMG2KW7	Back pain	ME84.Z	Approved	[16]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[17]
Decitabine	DMQL8XJ	Acute myelogenous leukaemia	2A41	Approved	[18]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[19]
Delphinidin	DMS2WIN	Cardiovascular disease	BA00-BE2Z	Phase 2	[20]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[21]
Milchsaure	DM462BT	Pruritus	EC90	Investigative	[22]

Drug(s) Affected By Type II iodothyronine deiodinase (DIO2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[23]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[24]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[25]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[26]
Methylprednisolone	DM4BDON	Acute adrenal insufficiency		Approved	[27]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[28]
Mifepristone	DMGZQEF	Cushing disease	5A70	Approved	[29]
Ergocalciferol	DMHO0AR	Hypoparathyroidism	5A50	Approved	[30]
Zoledronate	DMIXC7G	Adenocarcinoma	2D40	Approved	[31]
Temozolomide	DMKECZD	Adenocarcinoma	2D40	Approved	[32]

Drug(s) Affected By Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Quercetin	DM3NC4M	Obesity	5B81	Approved	[33]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[34]
Fructose	DM43AN2	Vomiting	MD90	Approved	[35]
Glucosamine	DM4ZLFD	Osteoarthritis	FA00-FA05	Approved	[36]
Isoniazid	DM5JVS3	Latent tuberculosis infection		Approved	[37]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[38]
Ketotifen	DM74XKS	Allergic conjunctivitis	9A60.02	Approved	[39]
Riboflavin	DM8YMWE	Acne vulgaris	ED80	Approved	[40]
Leflunomide	DMR8ONJ	Arthritis	FA20	Approved	[41]
Glutathione	DMAHMT9	Human immunodeficiency virus infection	1C62	Approved	[40]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Phosphodiesterase 10A (PDE10)	TTJW4LU	PDE10_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Lipid transferase CIDEA (CIDEA)	OTDUTSOV	CIDEA_HUMAN	Gene/Protein Processing	[3]
Mitochondrial brown fat uncoupling protein 1	OT0XMVWH	UCP1_HUMAN	Gene/Protein Processing	[3]
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A)	OTHCDQ22	PRGC1_HUMAN	Gene/Protein Processing	[3]
Type II iodothyronine deiodinase (DIO2)	OTGPNSLH	IOD2_HUMAN	Gene/Protein Processing	[3]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] ClinicalTrials.gov (NCT01939548) An Outpatient Study Of The Efficacy, Safety, And Tolerability Of PF-02545920 In The Adjunctive Treatment Of Sub-Optimally Controlled Symptoms of Schizophrenia. U.S. National Institutes of Health.
• [3] A novel thermoregulatory role for PDE10A in mouse and human adipocytes. EMBO Mol Med. 2016 Jul 1;8(7):796-812. doi: 10.15252/emmm.201506085. Print 2016 Jul.
• [4] The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis. J Neural Transm (Vienna). 2010 Nov;117(11):1319-25.
• [5] Characterization of Binding and Inhibitory Properties of TAK-063, a Novel Phosphodiesterase 10A Inhibitor. PLoS One. 2015; 10(3): e0122197.
• [6] New Drugs/Drug News. P T. 2013 November; 38(11): 667-672.
• [7] PDE10A Inhibitors-Clinical Failure or Window Into Antipsychotic Drug Action?. Front Neurosci. 2021 Jan 20;14:600178.
• [8] Massive schizophrenia genomics study offers new drug directions. Nat Rev Drug Discov. 2014 Sep;13(9):641-2.
• [9] Clinical pipeline report, company report or official report of Palobiofarma.
• [10] Synaptic synopsis. SciBX 6(41); doi:10.1038/scibx.2013.1153. Oct. 24, 2013
• [11] Discovery of clinical candidate 1-(4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)ethanone (AMG 579), a potent, selective, and efficacious inhibitor of phosphodiesterase10A (PDE10A). J Med Chem. 2014 Aug 14;57(15):6632-41.
• [12] Towards selective phosphodiesterase 2A (PDE2A) inhibitors: a patent review (2010 - present).Expert Opin Ther Pat. 2016 Aug;26(8):933-46.
• [13] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [14] Arsenic trioxide induces different gene expression profiles of genes related to growth and apoptosis in glioma cells dependent on the p53 status. Mol Biol Rep. 2008 Sep;35(3):421-9.
• [15] Effect of the Catechol-O-Methyltransferase Inhibitors Tolcapone and Entacapone on Fatty Acid Metabolism in HepaRG Cells. Toxicol Sci. 2018 Aug 1;164(2):477-488.
• [16] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [17] Dexamethasone and the inflammatory response in explants of human omental adipose tissue. Mol Cell Endocrinol. 2010 Feb 5;315(1-2):292-8.
• [18] CpG methylation plays a vital role in determining tissue- and cell-specific expression of the human cell-death-inducing DFF45-like effector A gene through the regulation of Sp1/Sp3 binding. Nucleic Acids Res. 2008 Jan;36(1):330-41. doi: 10.1093/nar/gkm1028. Epub 2007 Nov 22.
• [19] Pattern of expression of apoptosis and inflammatory genes in humans exposed to arsenic and/or fluoride. Sci Total Environ. 2010 Jan 15;408(4):760-7. doi: 10.1016/j.scitotenv.2009.11.016. Epub 2009 Dec 4.
• [20] Delphinidin modulates the DNA-damaging properties of topoisomerase II poisons. Chem Res Toxicol. 2009 Mar 16;22(3):554-64. doi: 10.1021/tx800293v.
• [21] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [22] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [23] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [24] The small polyphenolic molecule kaempferol increases cellular energy expenditure and thyroid hormone activation. Diabetes. 2007 Mar;56(3):767-76. doi: 10.2337/db06-1488.
• [25] Type 2 deiodinase expression is induced by peroxisomal proliferator-activated receptor-gamma agonists in skeletal myocytes. Endocrinology. 2009 Apr;150(4):1976-83. doi: 10.1210/en.2008-0938. Epub 2008 Nov 26.
• [26] Effects of all-trans and 9-cis retinoic acid on differentiating human neural stem cells in vitro. Toxicology. 2023 Mar 15;487:153461. doi: 10.1016/j.tox.2023.153461. Epub 2023 Feb 16.
• [27] Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
• [28] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [29] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [30] Screening the ToxCast Phase 1, Phase 2, and e1k Chemical Libraries for Inhibitors of Iodothyronine Deiodinases. Toxicol Sci. 2019 Apr 1;168(2):430-442. doi: 10.1093/toxsci/kfy302.
• [31] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [32] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [33] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [34] Troglitazone induces cytotoxicity in part by promoting the degradation of peroxisome proliferator-activated receptor co-activator-1 protein. Br J Pharmacol. 2010 Oct;161(4):771-81. doi: 10.1111/j.1476-5381.2010.00900.x.
• [35] Effects of four-week high-fructose diet on gene expression in skeletal muscle of healthy men. Diabetes Metab. 2008 Feb;34(1):82-5. doi: 10.1016/j.diabet.2007.08.004. Epub 2007 Dec 11.
• [36] Glucosamine-induced endoplasmic reticulum stress affects GLUT4 expression via activating transcription factor 6 in rat and human skeletal muscle cells. Diabetologia. 2010 May;53(5):955-65. doi: 10.1007/s00125-010-1676-1. Epub 2010 Feb 18.
• [37] AMPK activator acadesine fails to alleviate isoniazid-caused mitochondrial instability in HepG2 cells. J Appl Toxicol. 2017 Oct;37(10):1219-1224. doi: 10.1002/jat.3483. Epub 2017 May 29.
• [38] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [39] Advantageous use of HepaRG cells for the screening and mechanistic study of drug-induced steatosis. Toxicol Appl Pharmacol. 2016 Jul 1;302:1-9. doi: 10.1016/j.taap.2016.04.007. Epub 2016 Apr 16.
• [40] A cardiac-specific robotized cellular assay identified families of human ligands as inducers of PGC-1 expression and mitochondrial biogenesis. PLoS One. 2012;7(10):e46753. doi: 10.1371/journal.pone.0046753. Epub 2012 Oct 3.
• [41] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.