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

General Information of Drug (ID: DMQ94CT)

• Drug Name: AT9283 Drug Info

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 3	[1]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 135398495
  ChEBI ID: CHEBI:125514
  CAS Number: CAS 896466-04-9
  TTD Drug ID: DMQ94CT

Molecule-Related Drug Atlas

Drug(s) Targeting Aurora kinase B (AURKB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PHA-739358	DMGYBZI	Prostate cancer	2C82.0	Phase 2	[4]
VX-680	DM93YKJ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[5]
ABT-348	DMMZOYN	Haematological malignancy	2B33.Y	Phase 2	[6]
HPP-607	DM5VSZR	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
CYC116	DMUMHXT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
AMG 900	DMASGXJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
SNS-314	DMAC5F2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
BI-847325	DMY4B6J	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
R763	DME0CJ9	Haematological malignancy	2B33.Y	Phase 1	[12]
GSK1070916	DMXRPT6	Advanced solid tumour	2A00-2F9Z	Phase 1	[13]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[16]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[17]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[18]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[19]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[20]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[21]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[22]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[22]
Leflunomide	DMR8ONJ	Arthritis	FA20	Approved	[23]
Clodronate	DM9Y6X7	Hypercalcaemia	5B91.0	Approved	[24]

Drug(s) Targeting Aurora kinase A (AURKA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MLN8237	DMO8PT9	Solid tumour/cancer	2A00-2F9Z	Phase 3	[14]
PHA-739358	DMGYBZI	Prostate cancer	2C82.0	Phase 2	[4]
VX-680	DM93YKJ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[5]
ABT-348	DMMZOYN	Haematological malignancy	2B33.Y	Phase 2	[6]
ENMD-2076	DMJZVPB	Acute myeloid leukaemia	2A60	Phase 2	[4]
LY3295668	DM8RJTB	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[15]
HPP-607	DM5VSZR	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
MLN8054	DMUANF3	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
CYC116	DMUMHXT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
AMG 900	DMASGXJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]

Drug(s) Affected By Signal transducer and activator of transcription 5B (STAT5B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[25]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[26]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[27]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[28]
Quizartinib	DM8Y4JS	Acute myeloid leukaemia	2A60	Approved	[29]
Tofacitinib	DMBS370	Rheumatoid arthritis	FA20	Approved	[30]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[31]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[32]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[33]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[34]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Aurora kinase A (AURKA)	TTPS3C0	AURKA_HUMAN	Modulator	[2]
Aurora kinase B (AURKB)	TT5LS6T	AURKB_HUMAN	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Aurora kinase B (AURKB)	OTIY4VHU	AURKB_HUMAN	Post-Translational Modifications	[3]
Signal transducer and activator of transcription 5B (STAT5B)	OTZVPEBT	STA5B_HUMAN	Post-Translational Modifications	[3]

References

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• [2] A phase I trial of AT9283 (a selective inhibitor of aurora kinases) in children and adolescents with solid tumors: a Cancer Research UK study. Clin Cancer Res. 2015 Jan 15;21(2):267-73.
• [3] STAT5BN642H is a driver mutation for T cell neoplasia. J Clin Invest. 2018 Jan 2;128(1):387-401. doi: 10.1172/JCI94509. Epub 2017 Dec 4.
• [4] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [5] A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
• [6] Preclinical characterization of ABT-348, a kinase inhibitor targeting the aurora, vascular endothelial growth factor receptor/platelet-derived growth factor receptor, and Src kinase families. J Pharmacol Exp Ther. 2012 Dec;343(3):617-27.
• [7] 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: 1936).
• [8] Clinical pipeline report, company report or official report of Cyclacel.
• [9] Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines. Cancer Res. 2010 Dec 1;70(23):9846-54.
• [10] SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol. 2010 Mar;65(4):707-17.
• [11] doi: 10.1158/1535-7163.TARG-13-B281
• [12] Preclinical characterization of Aurora kinase inhibitor R763/AS703569 identified through an image-based phenotypic screen. J Cancer Res Clin Oncol. 2010 Jan;136(1):99-113.
• [13] Discovery of GSK1070916, a potent and selective inhibitor of Aurora B/C kinase. J Med Chem. 2010 May 27;53(10):3973-4001.
• [14] Effect of Aurora A kinase inhibitor MLN8237 combined with rituximab on antitumor activity in preclinical B-cell non-Hodgkin's lymphoma models. Journal of Clinical Oncology, 2009:8553.
• [15] Aurora A-Selective Inhibitor LY3295668 Leads to Dominant Mitotic Arrest, Apoptosis in Cancer Cells, and Shows Potent Preclinical Antitumor Efficacy. Mol Cancer Ther. 2019 Dec;18(12):2207-2219.
• [16] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [17] mTOR inhibition reverses acquired endocrine therapy resistance of breast cancer cells at the cell proliferation and gene-expression levels. Cancer Sci. 2008 Oct;99(10):1992-2003. doi: 10.1111/j.1349-7006.2008.00955.x.
• [18] Gene expression after treatment with hydrogen peroxide, menadione, or t-butyl hydroperoxide in breast cancer cells. Cancer Res. 2002 Nov 1;62(21):6246-54.
• [19] Synthesis and antitumor evaluation of nitrovinyl biphenyls: anticancer agents based on allocolchicines. ChemMedChem. 2011 May 2;6(5):859-68. doi: 10.1002/cmdc.201100019. Epub 2011 Apr 6.
• [20] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [21] Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
• [22] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [23] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [24] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [25] Oxidative stress triggers STAT3 tyrosine phosphorylation and nuclear translocation in human lymphocytes. J Biol Chem. 1999 Jun 18;274(25):17580-6. doi: 10.1074/jbc.274.25.17580.
• [26] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [27] Arsenic trioxide down-regulates antiapoptotic genes and induces cell death in mycosis fungoides tumors in a mouse model. Ann Oncol. 2008 Aug;19(8):1488-1494. doi: 10.1093/annonc/mdn056. Epub 2008 Mar 17.
• [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] BET protein antagonist JQ1 is synergistically lethal with FLT3 tyrosine kinase inhibitor (TKI) and overcomes resistance to FLT3-TKI in AML cells expressing FLT-ITD. Mol Cancer Ther. 2014 Oct;13(10):2315-27. doi: 10.1158/1535-7163.MCT-14-0258. Epub 2014 Jul 22.
• [30] Janus kinase 3-activating mutations identified in natural killer/T-cell lymphoma. Cancer Discov. 2012 Jul;2(7):591-7. doi: 10.1158/2159-8290.CD-12-0028. Epub 2012 Jun 15.
• [31] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [32] Differential effect of dexamethasone on cell death and STAT5 activation during in vitro eosinopoiesis. Br J Haematol. 2003 Dec;123(5):933-41. doi: 10.1046/j.1365-2141.2003.04700.x.
• [33] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [34] Progesterone pre-treatment potentiates EGF pathway signaling in the breast cancer cell line ZR-75. Breast Cancer Res Treat. 2005 Nov;94(2):171-83. doi: 10.1007/s10549-005-7726-6.