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

General Information of Drug (ID: DMVEBT6)

• Drug Name: CHIR-98014 Drug Info
• Synonyms: CHIR98014; CHIR 98014

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 53396311
  CAS Number: CAS 252935-94-7
  TTD Drug ID: DMVEBT6

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	[2]
TDZD-8	DMG6Q45	Malignant glioma	2A00.0	Patented	[11]
AR-A014418	DMUPN01	Ovarian cancer	2C73	Patented	[12]

Drug(s) Targeting GSK3A messenger RNA (GSK3A mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
aloisine A	DM5U1LN	Discovery agent	N.A.	Investigative	[13]
indirubin deriv. 8a	DMYLVQF	Discovery agent	N.A.	Investigative	[14]
LEUCETTAMINE B	DMFQEWM	Discovery agent	N.A.	Investigative	[15]
ISIS 116625	DMIJES1	Discovery agent	N.A.	Investigative	[16]
ISIS 116648	DMUOB3S	Discovery agent	N.A.	Investigative	[16]
ISIS 116632	DMW2Q4T	Discovery agent	N.A.	Investigative	[16]
ISIS 116631	DM2X5RT	Discovery agent	N.A.	Investigative	[16]
ISIS 116670	DM9R51M	Discovery agent	N.A.	Investigative	[16]
ISIS 116654	DMBJU2X	Discovery agent	N.A.	Investigative	[16]

Drug(s) Affected By Paired box protein Pax-6 (PAX6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[17]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[18]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[19]
Thalidomide	DM70BU5	Adult T-cell leukemia/lymphoma		Approved	[18]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[20]
Nilotinib	DM7HXWT	Chronic myelogenous leukaemia	2A20.0	Approved	[18]
Ramelteon	DM7IW9J	Insomnia	7A00-7A0Z	Approved	[18]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[21]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[3]
Dabigatran	DMDI6R4	Stroke	8B20	Approved	[18]

Drug(s) Affected By Homeobox protein OTX2 (OTX2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[17]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[3]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[22]
Carbamazepine	DMZOLBI	Epilepsy	8A60-8A68	Approved	[23]
Triclosan	DMZUR4N	Malaria	1F40-1F45	Approved	[24]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[25]
bisphenol A	DM2ZLD7	Discovery agent	N.A.	Investigative	[26]
Trichostatin A	DM9C8NX	Solid tumour/cancer	2A00-2F9Z	Investigative	[3]

Drug(s) Affected By Homeobox protein NANOG (NANOG)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[27]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[28]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[29]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[30]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[19]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[31]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[32]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[33]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[34]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[35]

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]
GSK3A messenger RNA (GSK3A mRNA)	TTQWAU1	GSK3A_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Homeobox protein NANOG (NANOG)	OTUEY1FM	NANOG_HUMAN	Gene/Protein Processing	[3]
Homeobox protein OTX2 (OTX2)	OTTV05B1	OTX2_HUMAN	Gene/Protein Processing	[3]
Paired box protein Pax-6 (PAX6)	OTOC9876	PAX6_HUMAN	Gene/Protein Processing	[3]

References

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• [2] 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.
• [3] Epigenetic changes and disturbed neural development in a human embryonic stem cell-based model relating to the fetal valproate syndrome. Hum Mol Genet. 2012 Sep 15;21(18):4104-14. doi: 10.1093/hmg/dds239. Epub 2012 Jun 20.
• [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] 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.
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• [13] Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in complex with CDK2, enzyme selectivity, and cellular effects. J Med Chem. 2003 Jan 16;46(2):222-36.
• [14] Structural basis for the synthesis of indirubins as potent and selective inhibitors of glycogen synthase kinase-3 and cyclin-dependent kinases. J Med Chem. 2004 Feb 12;47(4):935-46.
• [15] Synthesis and preliminary biological evaluation of new derivatives of the marine alkaloid leucettamine B as kinase inhibitors. Eur J Med Chem. 2010 Feb;45(2):805-10.
• [16] US patent application no. 6,316,259, Antisense inhibition of glycogen synthase kinase 3 alpha expression.
• [17] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [18] Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells. Reprod Toxicol. 2020 Jan;91:74-91. doi: 10.1016/j.reprotox.2019.10.004. Epub 2019 Nov 8.
• [19] 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.
• [20] hiPSC-Based Model of Prenatal Exposure to Cannabinoids: Effect on Neuronal Differentiation. Front Mol Neurosci. 2020 Jul 6;13:119. doi: 10.3389/fnmol.2020.00119. eCollection 2020.
• [21] 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.
• [22] 5-Fluorouracil inhibits neural differentiation via Mfn1/2 reduction in human induced pluripotent stem cells. J Toxicol Sci. 2018;43(12):727-734. doi: 10.2131/jts.43.727.
• [23] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [24] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [25] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [26] Transcriptomic?pathway?and?benchmark dose analysis of Bisphenol A, Bisphenol S, Bisphenol F, and 3,3',5,5'-Tetrabromobisphenol A in H9 human embryonic stem cells. Toxicol In Vitro. 2021 Apr;72:105097. doi: 10.1016/j.tiv.2021.105097. Epub 2021 Jan 18.
• [27] Methylparaben stimulates tumor initiating cells in ER+ breast cancer models. J Appl Toxicol. 2017 Apr;37(4):417-425. doi: 10.1002/jat.3374. Epub 2016 Sep 1.
• [28] Ciprofloxacin mediates cancer stem cell phenotypes in lung cancer cells through caveolin-1-dependent mechanism. Chem Biol Interact. 2016 Apr 25;250:1-11.
• [29] Quercetin in elimination of tumor initiating stem-like and mesenchymal transformation property in head and neck cancer. Head Neck. 2013 Mar;35(3):413-9. doi: 10.1002/hed.22982. Epub 2012 Mar 16.
• [30] Retinoic acid represses a cassette of candidate pluripotency chromosome 12p genes during induced loss of human embryonal carcinoma tumorigenicity. Biochim Biophys Acta. 2005 Oct 15;1731(1):48-56. doi: 10.1016/j.bbaexp.2005.08.006. Epub 2005 Sep 1.
• [31] The antipsychotic chlorpromazine suppresses YAP signaling, stemness properties, and drug resistance in breast cancer cells. Chem Biol Interact. 2019 Apr 1;302:28-35. doi: 10.1016/j.cbi.2019.01.033. Epub 2019 Jan 28.
• [32] Arsenic trioxide induces differentiation of cancer stem cells in hepatocellular carcinoma through inhibition of LIF/JAK1/STAT3 and NF-kB signaling pathways synergistically. Clin Transl Med. 2021 Feb;11(2):e335. doi: 10.1002/ctm2.335.
• [33] Altered expression of genes identified in rats with prostatic chronic inflammation in a prostate spheroid model treated by estradiol/testosterone. J Toxicol Sci. 2021;46(11):515-523. doi: 10.2131/jts.46.515.
• [34] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [35] Ivermectin as an inhibitor of cancer stem?like cells. Mol Med Rep. 2018 Feb;17(2):3397-3403. doi: 10.3892/mmr.2017.8231. Epub 2017 Dec 8.