Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCAS0OH)

• DOT Name: Kinetochore protein Spc25 (SPC25)
• Synonyms: hSpc25
• Gene Name: SPC25
• Related Disease:
  Hepatocellular carcinoma
  Advanced cancer
  Alzheimer disease
  Breast neoplasm
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Lung squamous cell carcinoma
  Non-small-cell lung cancer
  Prostate cancer
  Prostate carcinoma
  Breast cancer
  Breast carcinoma
• UniProt ID: SPC25_HUMAN
• PDB ID: 2VE7; 3IZ0
• Pfam ID: PF08234
• Sequence:
  MVEDELALFDKSINEFWNKFKSTDTSCQMAGLRDTYKDSIKAFAEKLSVKLKEEERMVEM
  FLEYQNQISRQNKLIQEKKDNLLKLIAEVKGKKQELEVLTANIQDLKEEYSRKKETISTA
  NKANAERLKRLQKSADLYKDRLGLEIRKIYGEKLQFIFTNIDPKNPESPFMFSLHLNEAR
  DYEVSDSAPHLEGLAEFQENVRKTNNFSAFLANVRKAFTATVYN
• 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.
• 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

13 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]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[4]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[2]
Lung cancer	DISCM4YA	Strong	Altered Expression	[5]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[5]
Lung squamous cell carcinoma	DISXPIBD	Strong	Biomarker	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Altered Expression	[6]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[6]
Breast cancer	DIS7DPX1	moderate	Biomarker	[7]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[7]

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 Spc25 (SPC25).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Kinetochore protein Spc25 (SPC25).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Kinetochore protein Spc25 (SPC25).	[34]

29 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 Spc25 (SPC25).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Kinetochore protein Spc25 (SPC25).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Kinetochore protein Spc25 (SPC25).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Kinetochore protein Spc25 (SPC25).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Kinetochore protein Spc25 (SPC25).	[13]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Kinetochore protein Spc25 (SPC25).	[14]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Kinetochore protein Spc25 (SPC25).	[15]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Kinetochore protein Spc25 (SPC25).	[17]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Kinetochore protein Spc25 (SPC25).	[18]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Kinetochore protein Spc25 (SPC25).	[19]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Kinetochore protein Spc25 (SPC25).	[19]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Kinetochore protein Spc25 (SPC25).	[20]
Marinol	DM70IK5	Approved	Marinol increases the expression of Kinetochore protein Spc25 (SPC25).	[21]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Kinetochore protein Spc25 (SPC25).	[22]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Kinetochore protein Spc25 (SPC25).	[23]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Kinetochore protein Spc25 (SPC25).	[24]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Kinetochore protein Spc25 (SPC25).	[25]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Kinetochore protein Spc25 (SPC25).	[26]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Kinetochore protein Spc25 (SPC25).	[27]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Kinetochore protein Spc25 (SPC25).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Kinetochore protein Spc25 (SPC25).	[29]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Kinetochore protein Spc25 (SPC25).	[30]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Kinetochore protein Spc25 (SPC25).	[31]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Kinetochore protein Spc25 (SPC25).	[32]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Kinetochore protein Spc25 (SPC25).	[33]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Kinetochore protein Spc25 (SPC25).	[27]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Kinetochore protein Spc25 (SPC25).	[35]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Kinetochore protein Spc25 (SPC25).	[17]
ORG2058	DMH1M6N	Investigative	ORG2058 decreases the expression of Kinetochore protein Spc25 (SPC25).	[36]

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