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

General Information of Drug (ID: DMIM9N1)

• Drug Name: AZD-1080 Drug Info

Indication

Disease Entry	ICD 11	Status	REF
Alzheimer disease	8A20	Discontinued in Phase 1	[1]

• Cross-matching ID:
  PubChem CID: 135564570
  CAS Number: CAS 612487-72-6
  TTD Drug ID: DMIM9N1

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	[4]
LY2090314	DMTBFE4	Acute myeloid leukaemia	2A60	Phase 2	[5]
Lithium	DMZ3OU6	Bipolar disorder	6A60	Phase 2	[6]
Tideglusib	DME4LA1	Alzheimer disease	8A20	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]

Drug(s) Affected By E3 ubiquitin-protein ligase RNF144B (RNF144B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Rofecoxib	DM3P5DA	Osteoarthritis	FA00-FA05	Approved	[14]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[15]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[16]
Leflunomide	DMR8ONJ	Arthritis	FA20	Approved	[17]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[18]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[19]
Zoledronate	DMIXC7G	Adenocarcinoma	2D40	Approved	[20]
Melphalan	DMOLNHF	Hematologic disease	3C0Z	Approved	[21]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[22]
Indomethacin	DMSC4A7	Bursitis		Approved	[23]

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	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
E3 ubiquitin-protein ligase RNF144B (RNF144B)	OTN7FCDE	R144B_HUMAN	Protein Interaction/Cellular Processes	[3]

References

• [1] 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. (Ligand id: 7819).
• [2] AZD1080, a novel GSK3 inhibitor, rescues synaptic plasticity deficits in rodent brain and exhibits peripheral target engagement in humans.J Neurochem.2013 May;125(3):446-56.
• [3] Pir2/Rnf144b is a potential endometrial cancer biomarker that promotes cell proliferation. Cell Death Dis. 2018 May 1;9(5):504. doi: 10.1038/s41419-018-0521-1.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2014-2015).Expert Opin Ther Pat. 2017 Jun;27(6):657-666.
• [6] 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.
• [7] Evidence for irreversible inhibition of glycogen synthase kinase-3beta by tideglusib. J Biol Chem. 2012 Jan 6;287(2):893-904.
• [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] Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
• [15] 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.
• [16] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [17] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [18] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [19] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [20] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [21] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [22] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [23] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.