Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIY4VHU)

• DOT Name: Aurora kinase B (AURKB)
• Synonyms: EC 2.7.11.1; Aurora 1; Aurora- and IPL1-like midbody-associated protein 1; AIM-1; Aurora/IPL1-related kinase 2; ARK-2; Aurora-related kinase 2; STK-1; Serine/threonine-protein kinase 12; Serine/threonine-protein kinase 5; Serine/threonine-protein kinase aurora-B
• Gene Name: AURKB
• UniProt ID: AURKB_HUMAN
• PDB ID: 4AF3
• EC Number: 2.7.11.1
• Pfam ID: PF00069
• Sequence:
  MAQKENSYPWPYGRQTAPSGLSTLPQRVLRKEPVTPSALVLMSRSNVQPTAAPGQKVMEN
  SSGTPDILTRHFTIDDFEIGRPLGKGKFGNVYLAREKKSHFIVALKVLFKSQIEKEGVEH
  QLRREIEIQAHLHHPNILRLYNYFYDRRRIYLILEYAPRGELYKELQKSCTFDEQRTATI
  MEELADALMYCHGKKVIHRDIKPENLLLGLKGELKIADFGWSVHAPSLRRKTMCGTLDYL
  PPEMIEGRMHNEKVDLWCIGVLCYELLVGNPPFESASHNETYRRIVKVDLKFPASVPMGA
  QDLISKLLRHNPSERLPLAQVSAHPWVRANSRRVLPPSALQSVA
• Function: Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Involved in the bipolar attachment of spindle microtubules to kinetochores and is a key regulator for the onset of cytokinesis during mitosis. Required for central/midzone spindle assembly and cleavage furrow formation. Key component of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage: phosphorylates CHMP4C, leading to retain abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated at late cytokinesis. AURKB phosphorylates the CPC complex subunits BIRC5/survivin, CDCA8/borealin and INCENP. Phosphorylation of INCENP leads to increased AURKB activity. Other known AURKB substrates involved in centromeric functions and mitosis are CENPA, DES/desmin, GPAF, KIF2C, NSUN2, RACGAP1, SEPTIN1, VIM/vimentin, HASPIN, and histone H3. A positive feedback loop involving HASPIN and AURKB contributes to localization of CPC to centromeres. Phosphorylation of VIM controls vimentin filament segregation in cytokinetic process, whereas histone H3 is phosphorylated at 'Ser-10' and 'Ser-28' during mitosis (H3S10ph and H3S28ph, respectively). AURKB is also required for kinetochore localization of BUB1 and SGO1. Phosphorylation of p53/TP53 negatively regulates its transcriptional activity. Key regulator of active promoters in resting B- and T-lymphocytes: acts by mediating phosphorylation of H3S28ph at active promoters in resting B-cells, inhibiting RNF2/RING1B-mediated ubiquitination of histone H2A and enhancing binding and activity of the USP16 deubiquitinase at transcribed genes. Acts as an inhibitor of CGAS during mitosis: catalyzes phosphorylation of the N-terminus of CGAS during the G2-M transition, blocking CGAS liquid phase separation and activation, and thereby preventing CGAS-induced autoimmunity. Phosphorylates KRT5 during anaphase and telophase.
• Tissue Specificity: High level expression seen in the thymus. It is also expressed in the spleen, lung, testis, colon, placenta and fetal liver. Expressed during S and G2/M phase and expression is up-regulated in cancer cells during M phase.; [Isoform 3]: Not expressed in normal liver, high expression in metastatic liver.
• KEGG Pathway:
  Polycomb repressive complex (hsa03083)
  Cell cycle (hsa04110)
• Reactome Pathway:
  APC/C (R-HSA-174178)
  Separation of Sister Chromatids (R-HSA-2467813)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  SUMOylation of DNA replication proteins (R-HSA-4615885)
  RHO GTPases Activate Formins (R-HSA-5663220)
  Regulation of TP53 Activity through Phosphorylation (R-HSA-6804756)
  Mitotic Prometaphase (R-HSA-68877)
  Regulation of MECP2 expression and activity (R-HSA-9022692)
  EML4 and NUDC in mitotic spindle formation (R-HSA-9648025)
  Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal (R-HSA-141444)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Vinblastine	DM5TVS3	Approved	Aurora kinase B (AURKB) affects the response to substance of Vinblastine.	[42]

48 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 B (AURKB).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Aurora kinase B (AURKB).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Aurora kinase B (AURKB).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Aurora kinase B (AURKB).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Aurora kinase B (AURKB).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Aurora kinase B (AURKB).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Aurora kinase B (AURKB).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Aurora kinase B (AURKB).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Aurora kinase B (AURKB).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Aurora kinase B (AURKB).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Aurora kinase B (AURKB).	[11]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Aurora kinase B (AURKB).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Aurora kinase B (AURKB).	[7]
Menadione	DMSJDTY	Approved	Menadione decreases the expression of Aurora kinase B (AURKB).	[10]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Aurora kinase B (AURKB).	[12]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Aurora kinase B (AURKB).	[13]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Aurora kinase B (AURKB).	[14]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Aurora kinase B (AURKB).	[15]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Aurora kinase B (AURKB).	[16]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Aurora kinase B (AURKB).	[17]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Aurora kinase B (AURKB).	[18]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Aurora kinase B (AURKB).	[19]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Aurora kinase B (AURKB).	[7]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Aurora kinase B (AURKB).	[7]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Aurora kinase B (AURKB).	[7]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Aurora kinase B (AURKB).	[20]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Aurora kinase B (AURKB).	[21]
Colchicine	DM2POTE	Approved	Colchicine increases the expression of Aurora kinase B (AURKB).	[22]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the expression of Aurora kinase B (AURKB).	[7]
SR141716A	DMCO5JZ	Approved	SR141716A decreases the expression of Aurora kinase B (AURKB).	[23]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of Aurora kinase B (AURKB).	[24]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Aurora kinase B (AURKB).	[25]
Bardoxolone methyl	DMODA2X	Phase 3	Bardoxolone methyl decreases the activity of Aurora kinase B (AURKB).	[26]
Rebamipide	DM2GHCR	Phase 3	Rebamipide decreases the expression of Aurora kinase B (AURKB).	[27]
MLN8237	DMO8PT9	Phase 3	MLN8237 decreases the activity of Aurora kinase B (AURKB).	[28]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Aurora kinase B (AURKB).	[8]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Aurora kinase B (AURKB).	[30]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Aurora kinase B (AURKB).	[2]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Aurora kinase B (AURKB).	[31]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Aurora kinase B (AURKB).	[32]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Aurora kinase B (AURKB).	[34]
LY294002	DMY1AFS	Phase 1	LY294002 decreases the expression of Aurora kinase B (AURKB).	[35]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Aurora kinase B (AURKB).	[36]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Aurora kinase B (AURKB).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Aurora kinase B (AURKB).	[38]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Aurora kinase B (AURKB).	[30]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Aurora kinase B (AURKB).	[39]
I-BET151	DMYRUH2	Investigative	I-BET151 decreases the expression of Aurora kinase B (AURKB).	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
AT9283	DMQ94CT	Phase 3	AT9283 decreases the phosphorylation of Aurora kinase B (AURKB).	[29]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Aurora kinase B (AURKB).	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
ZM-447439	DMFP8WE	Investigative	ZM-447439 affects the localization of Aurora kinase B (AURKB).	[41]

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