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

General Information of Drug (ID: DME4LA1)

• Drug Name: Tideglusib Drug Info
• Synonyms: NP-031112; NP-12; NP031112; Tideglusib(NP-031112)

Indication

Disease Entry	ICD 11	Status	REF
Alzheimer disease	8A20	Phase 2	[1]
Osteosarcoma	2B51	Phase 2	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[3]

• Cross-matching ID:
  PubChem CID: 11313622
  ChEBI ID: CHEBI:147398
  CAS Number: CAS 865854-05-3
  TTD Drug ID: DME4LA1

Molecule-Related Drug Atlas

Drug(s) Targeting Glycogen synthase kinase-3 beta (GSK-3B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AMO-02	DMJRU3A	Myotonic dystrophy	8C71.0	Phase 2/3	[5]
LY2090314	DMTBFE4	Acute myeloid leukaemia	2A60	Phase 2	[6]
Lithium	DMZ3OU6	Bipolar disorder	6A60	Phase 2	[7]
9-ING-41	DM57TY3	Myelofibrosis	2A20.2	Phase 2	[8]
Neu-120	DMXKOUC	Parkinson disease	8A00.0	Phase 1/2	[9]
KENPAULLONE	DMAGVXW	Discovery agent	N.A.	Patented	[10]
CHIR-99021	DMB8MNU	Allergic inflammation	4A80-4A85	Patented	[11]
TDZD-8	DMG6Q45	Malignant glioma	2A00.0	Patented	[12]
AR-A014418	DMUPN01	Ovarian cancer	2C73	Patented	[13]
PMID26161698-Compound-18	DM6JVR5	N. A.	N. A.	Patented	[14]

Drug(s) Targeting COVID-19 papain-like proteinase (PL-PRO)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Disulfiram	DMCL2OK	Alcohol dependence	6C40.2	Approved	[3]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[15]
SPI-1005	DM6XFHS	Reperfusion injury	ND56.Z	Approved	[3]
PX-12	DMLVHAJ	Pancreatic cancer	2C10	Phase 2	[3]
Hexylcarbamoyl fluorouracil	DMYNPK8	Solid tumour/cancer	2A00-2F9Z	Withdrawn from market	[3]
PMID26868298-compound-N3	DMQFUCD	Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[3]
GRL0617	DMX9AGF	Coronavirus infection	1D92	Preclinical	[16]
Isoarnebin 4	DM0B7NO	Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[3]
PMID32321856-compound-11a	DMN39V6	Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[17]
PMID32321856-compound-11b	DM31QEY	Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[17]

Drug(s) Affected By Glycogen synthase kinase-3 beta (GSK3B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[18]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[19]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[20]
Selenium	DM25CGV	N. A.	N. A.	Approved	[21]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[22]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[23]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[24]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[25]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[26]
Glucosamine	DM4ZLFD	Osteoarthritis	FA00-FA05	Approved	[27]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Glycogen synthase kinase-3 beta (GSK-3B)	TTRSMW9	GSK3B_HUMAN	Inhibitor	[2]
COVID-19 papain-like proteinase (PL-PRO)	TTNHMO8	R1AB_SARS2 (819-2763)	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Glycogen synthase kinase-3 beta (GSK3B)	OTL3L14B	GSK3B_HUMAN	Gene/Protein Processing	[4]

References

• [1] A Phase II Trial of Tideglusib in Alzheimer's Disease. J Alzheimers Dis. 2015;45(1):75-88.
• [2] Evidence for irreversible inhibition of glycogen synthase kinase-3beta by tideglusib. J Biol Chem. 2012 Jan 6;287(2):893-904.
• [3] Structure of Mpro from COVID-19 virus and discovery of its inhibitors. Nature. 2020 Apr 9.
• [4] Regulation of the Nrf2 Pathway by Glycogen Synthase Kinase-3 in MPP?-Induced Cell Damage. Molecules. 2019 Apr 8;24(7):1377. doi: 10.3390/molecules24071377.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2014-2015).Expert Opin Ther Pat. 2017 Jun;27(6):657-666.
• [7] The GSK3 kinase inhibitor lithium produces unexpected hyperphosphorylation of -catenin, a GSK3 substrate, in human glioblastoma cells. Biol Open. 2018 Jan 26;7(1):bio030874.
• [8] 9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer. Sci Rep. 2019 Dec 27;9(1):19977.
• [9] Company report (Neurim Pharmaceuticals)
• [10] 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6.
• [11] Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes. 2003 Mar;52(3):588-95.
• [12] Identification of novel scaffold of benzothiazepinones as non-ATP competitive glycogen synthase kinase-3beta inhibitors through virtual screening. Bioorg Med Chem Lett. 2012 Dec 1;22(23):7232-6.
• [13] Fragment and knowledge-based design of selective GSK-3beta inhibitors using virtual screening models. Eur J Med Chem. 2009 Jun;44(6):2361-71.
• [14] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
• [15] ClinicalTrials.gov (NCT04361422) Isotretinoin in Treatment of COVID-19. U.S. National Institutes of Health.
• [16] Crystal structure of SARS-CoV-2 papain-like protease. Acta Pharm Sin B. 2021 Jan;11(1):237-245.
• [17] Structure-based Design of Antiviral Drug Candidates Targeting the SARS-CoV-2 Main Protease. Science. 2020 Apr 22;eabb4489.
• [18] Cannabidiol Modulates the Expression of Alzheimer's Disease-Related Genes in Mesenchymal Stem Cells. Int J Mol Sci. 2016 Dec 23;18(1):26. doi: 10.3390/ijms18010026.
• [19] Effects and mechanisms of betulinic acid on improving EGFR TKI-resistance of lung cancer cells. Environ Toxicol. 2018 Nov;33(11):1153-1159.
• [20] The protective effects of liraglutide on AD-like neurodegeneration induced by oxidative stress in human neuroblastoma SH-SY5Y cells. Chem Biol Interact. 2019 Sep 1;310:108688. doi: 10.1016/j.cbi.2019.06.001. Epub 2019 Jun 4.
• [21] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [22] Dysregulation of integrin-linked kinase (ILK) signaling in colonic polyposis. Oncogene. 2001 Sep 27;20(43):6250-7. doi: 10.1038/sj.onc.1204791.
• [23] Differential effects of simvastatin and pravastatin on expression of Alzheimer's disease-related genes in human astrocytes and neuronal cells. J Lipid Res. 2009 Oct;50(10):2095-102. doi: 10.1194/jlr.M900236-JLR200. Epub 2009 May 21.
• [24] Quercetin potentiates apoptosis by inhibiting nuclear factor-kappaB signaling in H460 lung cancer cells. Biol Pharm Bull. 2013;36(6):944-51. doi: 10.1248/bpb.b12-01004.
• [25] Suppression of NF-kappaB and GSK-3beta is involved in colon cancer cell growth inhibition by the PPAR agonist troglitazone. Chem Biol Interact. 2010 Oct 6;188(1):75-85. doi: 10.1016/j.cbi.2010.06.001. Epub 2010 Jun 9.
• [26] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [27] NGBR is required to ameliorate type 2 diabetes in mice by enhancing insulin sensitivity. J Biol Chem. 2021 Jan-Jun;296:100624. doi: 10.1016/j.jbc.2021.100624. Epub 2021 Apr 2.