Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS7D306)

• DOT Name: Kinetochore protein NDC80 homolog (NDC80)
• Synonyms: Highly expressed in cancer protein; Kinetochore protein Hec1; HsHec1; Kinetochore-associated protein 2; Retinoblastoma-associated protein HEC
• Gene Name: NDC80
• Related Disease:
  Adenocarcinoma
  Advanced cancer
  Bone osteosarcoma
  Breast neoplasm
  Carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Endometrium adenocarcinoma
  Esophageal squamous cell carcinoma
  Familial adenomatous polyposis
  Gastric cancer
  Glioma
  Hemangioma
  Hepatitis C virus infection
  Hydrocephalus
  Hyperinsulinemia
  Leukemia
  Liver cancer
  Lung cancer
  Lung carcinoma
  Neoplasm
  Osteosarcoma
  Ovarian cancer
  Sarcoidosis
  Stomach cancer
  Non-small-cell lung cancer
  Breast cancer
  Breast carcinoma
  Cervical cancer
  Cervical carcinoma
  Childhood kidney Wilms tumor
  Clear cell renal carcinoma
  Epithelial ovarian cancer
  Hepatocellular carcinoma
  Leiomyosarcoma
  Malignant pleural mesothelioma
  Malignant soft tissue neoplasm
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Sarcoma
  Tubular aggregate myopathy
  Wilms tumor
• UniProt ID: NDC80_HUMAN
• PDB ID: 2IGP; 2VE7; 3IZ0; 8G0P
• Pfam ID: PF18077 ; PF03801
• Sequence:
  MKRSSVSSGGAGRLSMQELRSQDVNKQGLYTPQTKEKPTFGKLSINKPTSERKVSLFGKR
  TSGHGSRNSQLGIFSSSEKIKDPRPLNDKAFIQQCIRQLCEFLTENGYAHNVSMKSLQAP
  SVKDFLKIFTFLYGFLCPSYELPDTKFEEEVPRIFKDLGYPFALSKSSMYTVGAPHTWPH
  IVAALVWLIDCIKIHTAMKESSPLFDDGQPWGEETEDGIMHNKLFLDYTIKCYESFMSGA
  DSFDEMNAELQSKLKDLFNVDAFKLESLEAKNRALNEQIARLEQEREKEPNRLESLRKLK
  ASLQGDVQKYQAYMSNLESHSAILDQKLNGLNEEIARVELECETIKQENTRLQNIIDNQK
  YSVADIERINHERNELQQTINKLTKDLEAEQQKLWNEELKYARGKEAIETQLAEYHKLAR
  KLKLIPKGAENSKGYDFEIKFNPEAGANCLVKYRAQVYVPLKELLNETEEEINKALNKKM
  GLEDTLEQLNAMITESKRSVRTLKEEVQKLDDLYQQKIKEAEEEDEKCASELESLEKHKH
  LLESTVNQGLSEAMNELDAVQREYQLVVQTTTEERRKVGNNLQRLLEMVATHVGSVEKHL
  EEQIAKVDREYEECMSEDLSENIKEIRDKYEKKATLIKSSEE
• Function: Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity. Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore. The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules. Plays a role in chromosome congression and is essential for the end-on attachment of the kinetochores to spindle microtubules.
• KEGG Pathway: Cell cycle (hsa04110)
• Reactome Pathway:
  Separation of Sister Chromatids (R-HSA-2467813)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  RHO GTPases Activate Formins (R-HSA-5663220)
  Mitotic Prometaphase (R-HSA-68877)
  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

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[3]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[4]
Carcinoma	DISH9F1N	Strong	Biomarker	[5]
Colon cancer	DISVC52G	Strong	Altered Expression	[6]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Endometrium adenocarcinoma	DISY6744	Strong	Biomarker	[8]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[9]
Familial adenomatous polyposis	DISW53RE	Strong	Posttranslational Modification	[10]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[11]
Glioma	DIS5RPEH	Strong	Biomarker	[12]
Hemangioma	DISDCGAG	Strong	Biomarker	[13]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[14]
Hydrocephalus	DISIZUF7	Strong	Biomarker	[15]
Hyperinsulinemia	DISIDWT6	Strong	Biomarker	[16]
Leukemia	DISNAKFL	Strong	Genetic Variation	[17]
Liver cancer	DISDE4BI	Strong	Biomarker	[18]
Lung cancer	DISCM4YA	Strong	Biomarker	[2]
Lung carcinoma	DISTR26C	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[3]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[19]
Sarcoidosis	DISE5B8Z	Strong	Biomarker	[20]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[11]
Non-small-cell lung cancer	DIS5Y6R9	Disputed	Biomarker	[21]
Breast cancer	DIS7DPX1	Limited	Biomarker	[22]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[22]
Cervical cancer	DISFSHPF	Limited	Biomarker	[23]
Cervical carcinoma	DIST4S00	Limited	Biomarker	[23]
Childhood kidney Wilms tumor	DIS0NMK3	Limited	Biomarker	[24]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[25]
Epithelial ovarian cancer	DIS56MH2	Limited	Altered Expression	[19]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[2]
Leiomyosarcoma	DIS6COXM	Limited	Altered Expression	[26]
Malignant pleural mesothelioma	DIST2R60	Limited	Biomarker	[27]
Malignant soft tissue neoplasm	DISTC6NO	Limited	Altered Expression	[26]
Ovarian neoplasm	DISEAFTY	Limited	Altered Expression	[19]
Prostate cancer	DISF190Y	Limited	Altered Expression	[28]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[28]
Sarcoma	DISZDG3U	Limited	Altered Expression	[26]
Tubular aggregate myopathy	DISC11WH	Limited	Altered Expression	[29]
Wilms tumor	DISB6T16	Limited	Biomarker	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Vinblastine	DM5TVS3	Approved	Kinetochore protein NDC80 homolog (NDC80) affects the response to substance of Vinblastine.	[66]

3 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 Kinetochore protein NDC80 homolog (NDC80).	[30]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Kinetochore protein NDC80 homolog (NDC80).	[39]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Kinetochore protein NDC80 homolog (NDC80).	[60]

35 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 Kinetochore protein NDC80 homolog (NDC80).	[31]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[32]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[33]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[34]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[35]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Kinetochore protein NDC80 homolog (NDC80).	[36]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[37]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[38]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[40]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Kinetochore protein NDC80 homolog (NDC80).	[41]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Kinetochore protein NDC80 homolog (NDC80).	[42]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[43]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[43]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[44]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Kinetochore protein NDC80 homolog (NDC80).	[45]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Kinetochore protein NDC80 homolog (NDC80).	[42]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[46]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[47]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[48]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Kinetochore protein NDC80 homolog (NDC80).	[49]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[50]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[51]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[52]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[53]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[54]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Kinetochore protein NDC80 homolog (NDC80).	[55]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[56]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[57]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[58]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[59]
Scriptaid	DM9JZ21	Preclinical	Scriptaid affects the expression of Kinetochore protein NDC80 homolog (NDC80).	[61]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[62]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[63]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Kinetochore protein NDC80 homolog (NDC80).	[64]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Kinetochore protein NDC80 homolog (NDC80).	[65]

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