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

General Information of Drug (ID: DM0GOUD)

• Drug Name: Urokinase Drug Info

Indication

Disease Entry	ICD 11	Status	REF
Myocardial infarction	BA41-BA43	Approved	[1]
Pulmonary embolism	BB00	Approved	[2]

• Therapeutic Class: Thrombolytic Agents
• Cross-matching ID:
  PubChem CID: 33309
  TTD Drug ID: DM0GOUD

Molecule-Related Drug Atlas

Drug(s) Targeting Urokinase-type plasminogen activator (PLAU)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pro-urokinase	DMGKT2L	Thrombin deficiency	3B14.Z	Approved	[5]
PAI-1	DMY2AEF	N. A.	N. A.	Phase 4	[6]
Amediplase	DM4FPM3	Myocardial infarction	BA41-BA43	Phase 3	[1]
Upamostat	DMFZULI	Breast cancer	2C60-2C65	Phase 2	[7]
Saruplase	DM1M0PR	Thrombosis	DB61-GB90	Phase 2	[8]
HTU-PA	DMNHE43	Cerebrovascular ischaemia	8B1Z	Phase 1/2	[9]
PMID18163548C4	DMHPME3	Myocardial ischemia	BA6Z	Clinical trial	[10]
UK-356202	DMSRK2A	Myocardial hypertrophy	BC45	Clinical trial	[11]
PAI-2	DMRSMW8	N. A.	N. A.	Discontinued in Phase 2	[12]
WX-UK1	DM8Q2ZR	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1/2	[13]

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	[14]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[15]
Carvedilol	DMHTEAO	Chronic heart failure	BD1Z	Approved	[16]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[17]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[18]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[19]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[20]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[21]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[22]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[23]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Urokinase-type plasminogen activator (PLAU)	TTGY7WI	UROK_HUMAN	Modulator	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Drug Response	[4]

References

• [1] Emerging drugs in peripheral arterial disease. Expert Opin Emerg Drugs. 2006 Mar;11(1):75-90.
• [2] Comparative Efficacy and Safety of Thrombolytic Agents for Pulmonary Embolism: A Bayesian Network Meta-Analysis. Pharmacology. 2023;108(2):111-126.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] 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.
• [5] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2393).
• [6] Urokinase-type plasminogen activator and its inhibitor PAI-1: predictors of poor response to tamoxifen therapy in recurrent breast cancer. J Natl Cancer Inst. 1995 May 17;87(10):751-6.
• [7] Phase II randomised proof-of-concept study of the urokinase inhibitor upamostat (WX-671) in combination with gemcitabine compared with gemcitabine alone in patients with non-resectable, locally advanced pancreatic cancer. Br J Cancer. 2013 Mar 5;108(4):766-70.
• [8] Pharmacokinetics and pharmacodynamics of saruplase, an unglycosylated single-chain urokinase-type plasminogen activator, in patients with acute myocardial infarction. Thromb Haemost. 1994 Nov;72(5):740-4.
• [9] Characterization of the dexamethasone-induced inhibitor of plasminogen activator in HTC hepatoma cells. J Biol Chem. 1986 Mar 25;261(9):4352-7.
• [10] Fragment-based discovery of mexiletine derivatives as orally bioavailable inhibitors of urokinase-type plasminogen activator. J Med Chem. 2008 Jan 24;51(2):183-6.
• [11] Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 3: 1-isoquinolinylguanidines. Bioorg Med Chem Lett. 2004 Jun 21;14(12):3227-30.
• [12] Topological localization of plasminogen activator inhibitor type 2. Cytometry. 2000 May 1;40(1):32-41.
• [13] Inhibition of the invasion capacity of carcinoma cells by WX-UK1, a novel synthetic inhibitor of the urokinase-type plasminogen activator system. Int J Cancer. 2004 Jul 20;110(6):815-24.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] 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.
• [23] 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.