Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ8G3NP)

• DOT Name: Kinesin-like protein KIF2C (KIF2C)
• Synonyms: Kinesin-like protein 6; Mitotic centromere-associated kinesin; MCAK
• Gene Name: KIF2C
• Related Disease:
  Hepatocellular carcinoma
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Coronary atherosclerosis
  Gastric cancer
  Gastric neoplasm
  Glioma
  Her2-receptor negative breast cancer
  HER2/NEU overexpressing breast cancer
  Lung adenocarcinoma
  Myocardial infarction
  Neoplasm
  Non-small-cell lung cancer
  Osteoarthritis
  Stomach cancer
  Lung cancer
  Lung carcinoma
  Type-1/2 diabetes
  Contact dermatitis
  Coronary heart disease
• UniProt ID: KIF2C_HUMAN
• PDB ID: 2HEH; 4UBF; 4Y05; 5MIO
• Pfam ID: PF00225
• Sequence:
  MAMDSSLQARLFPGLAIKIQRSNGLIHSANVRTVNLEKSCVSVEWAEGGATKGKEIDFDD
  VAAINPELLQLLPLHPKDNLPLQENVTIQKQKRRSVNSKIPAPKESLRSRSTRMSTVSEL
  RITAQENDMEVELPAAANSRKQFSVPPAPTRPSCPAVAEIPLRMVSEEMEEQVHSIRGSS
  SANPVNSVRRKSCLVKEVEKMKNKREEKKAQNSEMRMKRAQEYDSSFPNWEFARMIKEFR
  ATLECHPLTMTDPIEEHRICVCVRKRPLNKQELAKKEIDVISIPSKCLLLVHEPKLKVDL
  TKYLENQAFCFDFAFDETASNEVVYRFTARPLVQTIFEGGKATCFAYGQTGSGKTHTMGG
  DLSGKAQNASKGIYAMASRDVFLLKNQPCYRKLGLEVYVTFFEIYNGKLFDLLNKKAKLR
  VLEDGKQQVQVVGLQEHLVNSADDVIKMIDMGSACRTSGQTFANSNSSRSHACFQIILRA
  KGRMHGKFSLVDLAGNERGADTSSADRQTRMEGAEINKSLLALKECIRALGQNKAHTPFR
  ESKLTQVLRDSFIGENSRTCMIATISPGISSCEYTLNTLRYADRVKELSPHSGPSGEQLI
  QMETEEMEACSNGALIPGNLSKEEEELSSQMSSFNEAMTQIRELEEKAMEELKEIIQQGP
  DWLELSEMTEQPDYDLETFVNKAESALAQQAKHFSALRDVIKALRLAMQLEEQASRQISS
  KKRPQ
• Function: In complex with KIF18B, constitutes the major microtubule plus-end depolymerizing activity in mitotic cells. Regulates the turnover of microtubules at the kinetochore and functions in chromosome segregation during mitosis. Plays a role in chromosome congression and is required for the lateral to end-on conversion of the chromosome-microtubule attachment.
• Tissue Specificity: Expressed at high levels in thymus and testis, at low levels in small intestine, the mucosal lining of colon, and placenta, and at very low levels in spleen and ovary; expression is not detected in prostate, peripheral blood Leukocytes, heart, brain, lung, liver, skeletal muscle, kidney or pancreas. Isoform 2 is testis-specific.
• KEGG Pathway: Motor proteins (hsa04814)
• Reactome Pathway:
  MHC class II antigen presentation (R-HSA-2132295)
  Separation of Sister Chromatids (R-HSA-2467813)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  RHO GTPases Activate Formins (R-HSA-5663220)
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  Mitotic Prometaphase (R-HSA-68877)
  EML4 and NUDC in mitotic spindle formation (R-HSA-9648025)
  Kinesins (R-HSA-983189)
  Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal (R-HSA-141444)

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Colon cancer	DISVC52G	Strong	Altered Expression	[4]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[5]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[6]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[7]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[8]
Gastric neoplasm	DISOKN4Y	Strong	Altered Expression	[8]
Glioma	DIS5RPEH	Strong	Altered Expression	[9]
Her2-receptor negative breast cancer	DISS605N	Strong	Biomarker	[10]
HER2/NEU overexpressing breast cancer	DISYKID5	Strong	Biomarker	[10]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[11]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[12]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[13]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[2]
Osteoarthritis	DIS05URM	Strong	Biomarker	[14]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[8]
Lung cancer	DISCM4YA	moderate	Altered Expression	[15]
Lung carcinoma	DISTR26C	moderate	Altered Expression	[15]
Type-1/2 diabetes	DISIUHAP	moderate	Genetic Variation	[16]
Contact dermatitis	DISQ3AU0	Limited	Biomarker	[17]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Kinesin-like protein KIF2C (KIF2C) affects the response to substance of Fluorouracil.	[52]

32 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 Kinesin-like protein KIF2C (KIF2C).	[18]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Kinesin-like protein KIF2C (KIF2C).	[19]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Kinesin-like protein KIF2C (KIF2C).	[20]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Kinesin-like protein KIF2C (KIF2C).	[21]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Kinesin-like protein KIF2C (KIF2C).	[22]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Kinesin-like protein KIF2C (KIF2C).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Kinesin-like protein KIF2C (KIF2C).	[24]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Kinesin-like protein KIF2C (KIF2C).	[25]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Kinesin-like protein KIF2C (KIF2C).	[26]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Kinesin-like protein KIF2C (KIF2C).	[27]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Kinesin-like protein KIF2C (KIF2C).	[29]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Kinesin-like protein KIF2C (KIF2C).	[29]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Kinesin-like protein KIF2C (KIF2C).	[30]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Kinesin-like protein KIF2C (KIF2C).	[31]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Kinesin-like protein KIF2C (KIF2C).	[32]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of Kinesin-like protein KIF2C (KIF2C).	[33]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Kinesin-like protein KIF2C (KIF2C).	[34]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Kinesin-like protein KIF2C (KIF2C).	[35]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Kinesin-like protein KIF2C (KIF2C).	[36]
Isoflavone	DM7U58J	Phase 4	Isoflavone decreases the expression of Kinesin-like protein KIF2C (KIF2C).	[37]
Genistein	DM0JETC	Phase 2/3	Genistein affects the expression of Kinesin-like protein KIF2C (KIF2C).	[38]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Kinesin-like protein KIF2C (KIF2C).	[39]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Kinesin-like protein KIF2C (KIF2C).	[40]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Kinesin-like protein KIF2C (KIF2C).	[41]
TAK-114	DMTXE19	Phase 1	TAK-114 decreases the expression of Kinesin-like protein KIF2C (KIF2C).	[43]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Kinesin-like protein KIF2C (KIF2C).	[44]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Kinesin-like protein KIF2C (KIF2C).	[46]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Kinesin-like protein KIF2C (KIF2C).	[48]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Kinesin-like protein KIF2C (KIF2C).	[49]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Kinesin-like protein KIF2C (KIF2C).	[50]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Kinesin-like protein KIF2C (KIF2C).	[51]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate increases the expression of Kinesin-like protein KIF2C (KIF2C).	[43]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the localization of Kinesin-like protein KIF2C (KIF2C).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Kinesin-like protein KIF2C (KIF2C).	[42]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Kinesin-like protein KIF2C (KIF2C).	[45]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Kinesin-like protein KIF2C (KIF2C).	[47]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Kinesin-like protein KIF2C (KIF2C).	[45]

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