Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMX0HYT)

• DOT Name: Aurora kinase A (AURKA)
• Synonyms: EC 2.7.11.1; Aurora 2; Aurora/IPL1-related kinase 1; ARK-1; Aurora-related kinase 1; Breast tumor-amplified kinase; Ipl1- and aurora-related kinase 1; Serine/threonine-protein kinase 15; Serine/threonine-protein kinase 6; Serine/threonine-protein kinase Ayk1; Serine/threonine-protein kinase aurora-A
• Gene Name: AURKA
• Related Disease:
  Breast cancer
  Intellectual disability
• UniProt ID: AURKA_HUMAN
• PDB ID: 1MQ4 ; 1MUO ; 1OL5 ; 1OL6 ; 1OL7 ; 2BMC ; 2C6D ; 2C6E ; 2DWB ; 2J4Z ; 2J50 ; 2NP8 ; 2W1C ; 2W1D ; 2W1E ; 2W1F ; 2W1G ; 2WQE ; 2WTV ; 2WTW ; 2X6D ; 2X6E ; 2X81 ; 2XNE ; 2XNG ; 2XRU ; 3COH ; 3E5A ; 3EFW ; 3FDN ; 3H0Y ; 3H0Z ; 3H10 ; 3HA6 ; 3K5U ; 3LAU ; 3M11 ; 3MYG ; 3NRM ; 3O50 ; 3O51 ; 3P9J ; 3QBN ; 3R21 ; 3R22 ; 3UNZ ; 3UO4 ; 3UO5 ; 3UO6 ; 3UOD ; 3UOH ; 3UOJ ; 3UOK ; 3UOL ; 3UP2 ; 3UP7 ; 3VAP ; 3W10 ; 3W16 ; 3W18 ; 3W2C ; 4B0G ; 4BN1 ; 4BYI ; 4BYJ ; 4C3P ; 4C3R ; 4CEG ; 4DEA ; 4DEB ; 4DED ; 4DEE ; 4DHF ; 4J8M ; 4J8N ; 4JAI ; 4JAJ ; 4JBO ; 4JBP ; 4JBQ ; 4O0S ; 4O0U ; 4O0W ; 4PRJ ; 4UYN ; 4UZD ; 4UZH ; 4ZS0 ; 4ZTQ ; 4ZTR ; 4ZTS ; 5AAD ; 5AAE ; 5AAF ; 5AAG ; 5DN3 ; 5DNR ; 5DOS ; 5DPV ; 5DR2 ; 5DR6 ; 5DR9 ; 5DRD ; 5DT0 ; 5DT3 ; 5DT4 ; 5EW9 ; 5G15 ; 5G1X ; 5L8J ; 5L8K ; 5L8L ; 5LXM ; 5OBJ ; 5OBR ; 5ODT ; 5ONE ; 5ORL ; 5ORN ; 5ORO ; 5ORP ; 5ORR ; 5ORS ; 5ORT ; 5ORV ; 5ORW ; 5ORX ; 5ORY ; 5ORZ ; 5OS0 ; 5OS1 ; 5OS2 ; 5OS3 ; 5OS4 ; 5OS5 ; 5OS6 ; 5OSD ; 5OSE ; 5OSF ; 5ZAN ; 6C2R ; 6C2T ; 6C83 ; 6CPE ; 6CPF ; 6CPG ; 6GRA ; 6HJJ ; 6HJK ; 6I2U ; 6R49 ; 6R4A ; 6R4B ; 6R4C ; 6R4D ; 6VPG ; 6VPH ; 6VPI ; 6VPJ ; 6VPL ; 6VPM ; 6XKA ; 6Z4Y ; 7AYH ; 7AYI ; 7FIC ; 7O2V ; 7ZTL ; 8GUW ; 8JMX ; 8SSO ; 8SSP
• EC Number: 2.7.11.1
• Pfam ID: PF00069
• Sequence:
  MDRSKENCISGPVKATAPVGGPKRVLVTQQFPCQNPLPVNSGQAQRVLCPSNSSQRIPLQ
  AQKLVSSHKPVQNQKQKQLQATSVPHPVSRPLNNTQKSKQPLPSAPENNPEEELASKQKN
  EESKKRQWALEDFEIGRPLGKGKFGNVYLAREKQSKFILALKVLFKAQLEKAGVEHQLRR
  EVEIQSHLRHPNILRLYGYFHDATRVYLILEYAPLGTVYRELQKLSKFDEQRTATYITEL
  ANALSYCHSKRVIHRDIKPENLLLGSAGELKIADFGWSVHAPSSRRTTLCGTLDYLPPEM
  IEGRMHDEKVDLWSLGVLCYEFLVGKPPFEANTYQETYKRISRVEFTFPDFVTEGARDLI
  SRLLKHNPSQRPMLREVLEHPWITANSSKPSNCQNKESASKQS
• Function: Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis. Required for normal spindle positioning during mitosis and for the localization of NUMA1 and DCTN1 to the cell cortex during metaphase. Required for initial activation of CDK1 at centrosomes. Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2. Regulates KIF2A tubulin depolymerase activity. Important for microtubule formation and/or stabilization. Required for normal axon formation. Plays a role in microtubule remodeling during neurite extension. Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and destabilizing p53/TP53. Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity. Inhibits cilia outgrowth. Required for cilia disassembly via phosphorylation of HDAC6 and subsequent deacetylation of alpha-tubulin. Regulates protein levels of the anti-apoptosis protein BIRC5 by suppressing the expression of the SCF(FBXL7) E3 ubiquitin-protein ligase substrate adapter FBXL7 through the phosphorylation of the transcription factor FOXP1.
• Tissue Specificity: Highly expressed in testis and weakly in skeletal muscle, thymus and spleen. Also highly expressed in colon, ovarian, prostate, neuroblastoma, breast and cervical cancer cell lines.
• KEGG Pathway:
  Oocyte meiosis (hsa04114)
  Progesterone-mediated oocyte maturation (hsa04914)
• Reactome Pathway:
  Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)
  SUMOylation of DNA replication proteins (R-HSA-4615885)
  TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest (R-HSA-6804114)
  Regulation of TP53 Activity through Phosphorylation (R-HSA-6804756)
  FBXL7 down-regulates AURKA during mitotic entry and in early mitosis (R-HSA-8854050)
  AURKA Activation by TPX2 (R-HSA-8854518)
  Interaction between PHLDA1 and AURKA (R-HSA-8854521)
  APC/C (R-HSA-174178)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Limited	Autosomal dominant	[1]
Intellectual disability	DISMBNXP	Limited	Autosomal dominant	[1]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Aurora kinase A (AURKA) decreases the response to substance of Cisplatin.	[42]
Gefitinib	DM15F0X	Approved	Aurora kinase A (AURKA) decreases the response to substance of Gefitinib.	[43]

46 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Aurora kinase A (AURKA).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Aurora kinase A (AURKA).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Aurora kinase A (AURKA).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Aurora kinase A (AURKA).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Aurora kinase A (AURKA).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Aurora kinase A (AURKA).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Aurora kinase A (AURKA).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Aurora kinase A (AURKA).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Aurora kinase A (AURKA).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Aurora kinase A (AURKA).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Aurora kinase A (AURKA).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Aurora kinase A (AURKA).	[13]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Aurora kinase A (AURKA).	[13]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Aurora kinase A (AURKA).	[14]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Aurora kinase A (AURKA).	[15]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Aurora kinase A (AURKA).	[16]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Aurora kinase A (AURKA).	[6]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Aurora kinase A (AURKA).	[17]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Aurora kinase A (AURKA).	[18]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Aurora kinase A (AURKA).	[19]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Aurora kinase A (AURKA).	[20]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Aurora kinase A (AURKA).	[21]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Aurora kinase A (AURKA).	[22]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Aurora kinase A (AURKA).	[23]
Sulindac	DM2QHZU	Approved	Sulindac decreases the expression of Aurora kinase A (AURKA).	[19]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Aurora kinase A (AURKA).	[24]
Daunorubicin	DMQUSBT	Approved	Daunorubicin decreases the expression of Aurora kinase A (AURKA).	[25]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Aurora kinase A (AURKA).	[26]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Aurora kinase A (AURKA).	[28]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Aurora kinase A (AURKA).	[29]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Aurora kinase A (AURKA).	[8]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Aurora kinase A (AURKA).	[30]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Aurora kinase A (AURKA).	[17]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Aurora kinase A (AURKA).	[31]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Aurora kinase A (AURKA).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Aurora kinase A (AURKA).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Aurora kinase A (AURKA).	[34]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Aurora kinase A (AURKA).	[35]
AZD-1152-HQPA	DMMW72C	Phase 1	AZD-1152-HQPA decreases the activity of Aurora kinase A (AURKA).	[36]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Aurora kinase A (AURKA).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Aurora kinase A (AURKA).	[38]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Aurora kinase A (AURKA).	[30]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Aurora kinase A (AURKA).	[39]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Aurora kinase A (AURKA).	[28]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Aurora kinase A (AURKA).	[40]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Aurora kinase A (AURKA).	[41]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Felodipine	DMOSW35	Approved	Felodipine affects the binding of Aurora kinase A (AURKA).	[27]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
VX-680	DM93YKJ	Phase 2	VX-680 decreases the phosphorylation of Aurora kinase A (AURKA).	[33]

References

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