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

General Information of Drug (ID: DMI0UJS)

• Drug Name: JTP-4819 Drug Info
• Synonyms: JTP-3399

Indication

Disease Entry	ICD 11	Status	REF
Cognitive impairment	6D71	Discontinued in Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 178060
  CAS Number: CAS 162203-65-8
  TTD Drug ID: DMI0UJS

Molecule-Related Drug Atlas

Drug(s) Targeting Prolyl endopeptidase (PREP)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BAICALEIN	DM4C7E6	Influenza virus infection	1E30-1E32	Phase 2	[4]
ALV-003	DMXSFA0	Coeliac disease	DA95	Phase 2	[5]
ONO-1603	DMKIZAL	Cognitive impairment	6D71	Phase 2	[6]
S-17092-1	DMYR1K8	Cognitive impairment	6D71	Phase 1	[7]
Z-321	DMLO2QY	Parkinson disease	8A00.0	Discontinued in Phase 1	[8]
BAICALIN	DMY1TLZ	Human immunodeficiency virus infection	1C62	Terminated	[9]
Y-29794	DMLAVES	N. A.	N. A.	Terminated	[9]
Double Oxidized Cysteine	DM6TU84	Discovery agent	N.A.	Investigative	[10]
Monothioglycerol	DMENSOZ	Discovery agent	N.A.	Investigative	[10]
Z-Pro-Prolinal	DM43O2U	Discovery agent	N.A.	Investigative	[11]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[3]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[28]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[29]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[30]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[31]
Menadione	DMSJDTY	Vitamin K deficiency	5B59	Approved	[32]
Phenobarbital	DMXZOCG	Cluster headache	8A81.0	Approved	[33]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[34]
THAPSIGARGIN	DMDMQIE	N. A.	N. A.	Preclinical	[35]
bisphenol A	DM2ZLD7	Discovery agent	N.A.	Investigative	[36]

Drug(s) Affected By Mitogen-activated protein kinase 3 (MAPK3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[12]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[13]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[14]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[15]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[16]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[17]
Secobarbital	DM14RF5	Epilepsy	8A60-8A68	Approved	[18]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[19]
Fexofenadine	DM17ONX	Allergic rhinitis	CA08.0	Approved	[20]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[21]

Drug(s) Affected By Mitogen-activated protein kinase 1 (MAPK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[22]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[13]
Carvedilol	DMHTEAO	Chronic heart failure	BD1Z	Approved	[23]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[24]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[25]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[12]
Urokinase	DM0GOUD	Myocardial infarction	BA41-BA43	Approved	[26]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[27]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[15]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[16]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Prolyl endopeptidase (PREP)	TTNGKET	PPCE_HUMAN	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Post-Translational Modifications	[3]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Post-Translational Modifications	[3]
Prolyl endopeptidase (PREP)	OTSJZBB5	PPCE_HUMAN	Gene/Protein Processing	[3]

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006163)
• [2] A novel prolyl endopeptidase inhibitor, JTP-4819, with potential for treating Alzheimer's disease. Behav Brain Res. 1997 Feb;83(1-2):147-51.
• [3] Prolyl endopeptidase is involved in cellular signalling in human neuroblastoma SH-SY5Y cells. Neurosignals. 2011;19(2):97-109. doi: 10.1159/000326342. Epub 2011 Apr 10.
• [4] Baicalin, a prodrug able to reach the CNS, is a prolyl oligopeptidase inhibitor. Bioorg Med Chem. 2008 Aug 1;16(15):7516-24.
• [5] The effects of ALV003 pre-digestion of gluten on immune response and symptoms in celiac disease in vivo. Clin Immunol. 2010 Mar;134(3):289-95.
• [6] ONO-1603, a potential antidementia drug, shows neuroprotective effects and increases m3-muscarinic receptor mRNA levels in differentiating rat cerebellar granule neurons. Neurosci Lett. 1996 Aug 23;214(2-3):151-4.
• [7] Effect of S 17092, a novel prolyl endopeptidase inhibitor, on substance P and alpha-melanocyte-stimulating hormone breakdown in the rat brain. J Neurochem. 2003 Mar;84(5):919-29.
• [8] Z-321, a prolyl endopeptidase inhibitor, augments the potentiation of synaptic transmission in rat hippocampal slices. Behav Brain Res. 1997 Feb;83(1-2):213-6.
• [9] Inhibitors of prolyl oligopeptidases for the therapy of human diseases: defining diseases and inhibitors. J Med Chem. 2010 May 13;53(9):3423-38.
• [10] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [11] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [12] Treatment with anticancer agents induces dysregulation of specific Wnt signaling pathways in human ovarian luteinized granulosa cells in vitro. Toxicol Sci. 2013 Nov;136(1):183-92. doi: 10.1093/toxsci/kft175. Epub 2013 Aug 16.
• [13] Progesterone increases csk homologous kinase in HMC-1560 human mast cells and reduces cell proliferation. J Cell Biochem. 2007 Dec 1;102(5):1271-80. doi: 10.1002/jcb.21357.
• [14] Cannabidiol upregulates melanogenesis through CB1 dependent pathway by activating p38 MAPK and p42/44 MAPK. Chem Biol Interact. 2017 Aug 1;273:107-114. doi: 10.1016/j.cbi.2017.06.005. Epub 2017 Jun 7.
• [15] Sertraline, an antidepressant, induces apoptosis in hepatic cells through the mitogen-activated protein kinase pathway. Toxicol Sci. 2014 Feb;137(2):404-15. doi: 10.1093/toxsci/kft254. Epub 2013 Nov 5.
• [16] Growth stimulation of human pulmonary adenocarcinoma cells and small airway epithelial cells by beta-carotene via activation of cAMP, PKA, CREB and ERK1/2. Int J Cancer. 2006 Mar 15;118(6):1370-80. doi: 10.1002/ijc.21537.
• [17] Estrogen and pure antiestrogen fulvestrant (ICI 182 780) augment cell-matrigel adhesion of MCF-7 breast cancer cells through a novel G protein coupled estrogen receptor (GPR30)-to-calpain signaling axis. Toxicol Appl Pharmacol. 2014 Mar 1;275(2):176-81. doi: 10.1016/j.taap.2014.01.005. Epub 2014 Jan 17.
• [18] Inhibition of activator protein 1 by barbiturates is mediated by differential effects on mitogen-activated protein kinases and the small G proteins ras and rac-1. J Pharmacol Exp Ther. 2004 Dec;311(3):1232-40. doi: 10.1124/jpet.104.071332. Epub 2004 Jul 19.
• [19] Growth of hormone-dependent MCF-7 breast cancer cells is promoted by constitutive caveolin-1 whose expression is lost in an EGF-R-mediated manner during development of tamoxifen resistance. Breast Cancer Res Treat. 2010 Feb;119(3):575-91. doi: 10.1007/s10549-009-0355-8. Epub 2009 Mar 15.
• [20] Effect of histamine H1 receptor antagonists on TARC/CCL17 and MDC/CCL22 production from CD14+ cells induced by antigenic stimulation in vitro. Int Arch Allergy Immunol. 2011;155(1):38-51. doi: 10.1159/000318720. Epub 2010 Nov 25.
• [21] SIRT3 Mediates the Antioxidant Effect of Hydrogen Sulfide in Endothelial Cells. Antioxid Redox Signal. 2016 Feb 20;24(6):329-43. doi: 10.1089/ars.2015.6331. Epub 2015 Nov 10.
• [22] Downregulation of mitogen-activated protein kinases (MAPKs) in chronic ethanol-induced fatty liver. Toxicol Mech Methods. 2020 Jul;30(6):407-416. doi: 10.1080/15376516.2020.1747126. Epub 2020 Apr 1.
• [23] A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling. Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16657-62. doi: 10.1073/pnas.0707936104. Epub 2007 Oct 9.
• [24] The stent-eluting drugs sirolimus and paclitaxel suppress healing of the endothelium by induction of autophagy. Am J Pathol. 2009 Nov;175(5):2226-34.
• [25] Modulation of apoptosis in HaCaT keratinocytes via differential regulation of ERK signaling pathway by flavonoids. J Biol Chem. 2005 Sep 9;280(36):31498-507. doi: 10.1074/jbc.M505537200. Epub 2005 Jul 13.
• [26] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [27] Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
• [28] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [29] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [30] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [31] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [32] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [33] Proteomic analysis of hepatic effects of phenobarbital in mice with humanized liver. Arch Toxicol. 2022 Oct;96(10):2739-2754. doi: 10.1007/s00204-022-03338-7. Epub 2022 Jul 26.
• [34] Interindividual variation in gene expression responses and metabolite formation in acetaminophen-exposed primary human hepatocytes. Arch Toxicol. 2016 May;90(5):1103-15. doi: 10.1007/s00204-015-1545-2. Epub 2015 Jun 24.
• [35] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [36] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.