Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWLJYH0)

• DOT Name: Targeting protein for Xklp2 (TPX2)
• Synonyms: Differentially expressed in cancerous and non-cancerous lung cells 2; DIL-2; Hepatocellular carcinoma-associated antigen 519; Hepatocellular carcinoma-associated antigen 90; Protein fls353; Restricted expression proliferation-associated protein 100; p100
• Gene Name: TPX2
• Related Disease: Tourette syndrome
• UniProt ID: TPX2_HUMAN
• PDB ID: 1OL5; 3E5A; 3HA6; 4C3P; 5LXM; 6BJC; 6VPG; 6VPH; 6VPI; 6VPJ; 6VPL; 6VPM; 6XKA
• Pfam ID: PF09041 ; PF06886 ; PF12214
• Sequence:
  MSQVKSSYSYDAPSDFINFSSLDDEGDTQNIDSWFEEKANLENKLLGKNGTGGLFQGKTP
  LRKANLQQAIVTPLKPVDNTYYKEAEKENLVEQSIPSNACSSLEVEAAISRKTPAQPQRR
  SLRLSAQKDLEQKEKHHVKMKAKRCATPVIIDEILPSKKMKVSNNKKKPEEEGSAHQDTA
  EKNASSPEKAKGRHTVPCMPPAKQKFLKSTEEQELEKSMKMQQEVVEMRKKNEEFKKLAL
  AGIGQPVKKSVSQVTKSVDFHFRTDERIKQHPKNQEEYKEVNFTSELRKHPSSPARVTKG
  CTIVKPFNLSQGKKRTFDETVSTYVPLAQQVEDFHKRTPNRYHLRSKKDDINLLPSKSSV
  TKICRDPQTPVLQTKHRARAVTCKSTAELEAEELEKLQQYKFKARELDPRILEGGPILPK
  KPPVKPPTEPIGFDLEIEKRIQERESKKKTEDEHFEFHSRPCPTKILEDVVGVPEKKVLP
  ITVPKSPAFALKNRIRMPTKEDEEEDEPVVIKAQPVPHYGVPFKPQIPEARTVEICPFSF
  DSRDKERQLQKEKKIKELQKGEVPKFKALPLPHFDTINLPEKKVKNVTQIEPFCLETDRR
  GALKAQTWKHQLEEELRQQKEAACFKARPNTVISQEPFVPKKEKKSVAEGLSGSLVQEPF
  QLATEKRAKERQELEKRMAEVEAQKAQQLEEARLQEEEQKKEELARLRRELVHKANPIRK
  YQGLEIKSSDQPLTVPVSPKFSTRFHC
• Function: Spindle assembly factor required for normal assembly of mitotic spindles. Required for normal assembly of microtubules during apoptosis. Required for chromatin and/or kinetochore dependent microtubule nucleation. Mediates AURKA localization to spindle microtubules. Activates AURKA by promoting its autophosphorylation at 'Thr-288' and protects this residue against dephosphorylation. TPX2 is inactivated upon binding to importin-alpha. At the onset of mitosis, GOLGA2 interacts with importin-alpha, liberating TPX2 from importin-alpha, allowing TPX2 to activates AURKA kinase and stimulates local microtubule nucleation.
• Tissue Specificity: Expressed in lung carcinoma cell lines but not in normal lung tissues.
• Reactome Pathway:
  AURKA Activation by TPX2 (R-HSA-8854518)
  Regulation of TP53 Activity through Phosphorylation (R-HSA-6804756)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Tourette syndrome	DISX9D54	No Known	Unknown	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Josamycin	DMKJ8LB	Approved	Targeting protein for Xklp2 (TPX2) affects the response to substance of Josamycin.	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Targeting protein for Xklp2 (TPX2).	[2]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Targeting protein for Xklp2 (TPX2).	[28]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Targeting protein for Xklp2 (TPX2).	[31]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Targeting protein for Xklp2 (TPX2).	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Targeting protein for Xklp2 (TPX2).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Targeting protein for Xklp2 (TPX2).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Targeting protein for Xklp2 (TPX2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Targeting protein for Xklp2 (TPX2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Targeting protein for Xklp2 (TPX2).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Targeting protein for Xklp2 (TPX2).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Targeting protein for Xklp2 (TPX2).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Targeting protein for Xklp2 (TPX2).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Targeting protein for Xklp2 (TPX2).	[11]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Targeting protein for Xklp2 (TPX2).	[11]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Targeting protein for Xklp2 (TPX2).	[12]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Targeting protein for Xklp2 (TPX2).	[13]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Targeting protein for Xklp2 (TPX2).	[14]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Targeting protein for Xklp2 (TPX2).	[15]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Targeting protein for Xklp2 (TPX2).	[16]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Targeting protein for Xklp2 (TPX2).	[17]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Targeting protein for Xklp2 (TPX2).	[18]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Targeting protein for Xklp2 (TPX2).	[19]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Targeting protein for Xklp2 (TPX2).	[20]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Targeting protein for Xklp2 (TPX2).	[21]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Targeting protein for Xklp2 (TPX2).	[22]
Bicalutamide	DMZMSPF	Approved	Bicalutamide decreases the expression of Targeting protein for Xklp2 (TPX2).	[23]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Targeting protein for Xklp2 (TPX2).	[9]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Targeting protein for Xklp2 (TPX2).	[24]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Targeting protein for Xklp2 (TPX2).	[25]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Targeting protein for Xklp2 (TPX2).	[26]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Targeting protein for Xklp2 (TPX2).	[27]
TAK-114	DMTXE19	Phase 1	TAK-114 decreases the expression of Targeting protein for Xklp2 (TPX2).	[29]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Targeting protein for Xklp2 (TPX2).	[30]
NS398	DMINUWH	Terminated	NS398 decreases the expression of Targeting protein for Xklp2 (TPX2).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Targeting protein for Xklp2 (TPX2).	[33]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Targeting protein for Xklp2 (TPX2).	[24]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Targeting protein for Xklp2 (TPX2).	[9]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Targeting protein for Xklp2 (TPX2).	[34]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Targeting protein for Xklp2 (TPX2).	[35]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Targeting protein for Xklp2 (TPX2).	[36]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate increases the expression of Targeting protein for Xklp2 (TPX2).	[29]

References

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