Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3U0JF8)

• DOT Name: Cystatin-B (CSTB)
• Synonyms: CPI-B; Liver thiol proteinase inhibitor; Stefin-B
• Gene Name: CSTB
• Related Disease:
  Esophageal squamous cell carcinoma
  Unverricht-Lundborg syndrome
  Cardiovascular disease
  Cerebellar ataxia
  Childhood epilepsy with centrotemporal spikes
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Epilepsy
  Epithelial ovarian cancer
  Gastric cancer
  Hepatocellular carcinoma
  Intracranial meningioma
  Lafora disease
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Stomach cancer
  Glioblastoma multiforme
  Infantile spasm
  Intellectual disability
  Keratolytic winter erythema
  Movement disorder
  Progressive myoclonus epilepsy
  Autosomal recessive hypohidrotic ectodermal dysplasia
  Meningioma
  Abdominal aortic aneurysm
  Nervous system disease
• UniProt ID: CYTB_HUMAN
• PDB ID: 1STF; 2OCT; 4N6V
• Pfam ID: PF00031
• Sequence:
  MMCGAPSATQPATAETQHIADQVRSQLEEKENKKFPVFKAVSFKSQVVAGTNYFIKVHVG
  DEDFVHLRVFQSLPHENKPLTLSNYQTNKAKHDELTYF
• Function: This is an intracellular thiol proteinase inhibitor. Tightly binding reversible inhibitor of cathepsins L, H and B.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

32 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal squamous cell carcinoma	DIS5N2GV	Definitive	Biomarker	[1]
Unverricht-Lundborg syndrome	DISG4WLX	Definitive	Autosomal recessive	[2]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[3]
Cerebellar ataxia	DIS9IRAV	Strong	Genetic Variation	[4]
Childhood epilepsy with centrotemporal spikes	DISKT2L5	Strong	CausalMutation	[5]
Colon cancer	DISVC52G	Strong	Altered Expression	[6]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[6]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[6]
Epilepsy	DISBB28L	Strong	Biomarker	[7]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[8]
Gastric cancer	DISXGOUK	Strong	Biomarker	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[10]
Intracranial meningioma	DISD09EF	Strong	Biomarker	[11]
Lafora disease	DIS83JHH	Strong	Biomarker	[12]
Lung cancer	DISCM4YA	Strong	Altered Expression	[6]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[6]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[6]
Neoplasm	DISZKGEW	Strong	Altered Expression	[6]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[8]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[8]
Stomach cancer	DISKIJSX	Strong	Biomarker	[9]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[13]
Infantile spasm	DISZSKDG	Moderate	Autosomal recessive	[2]
Intellectual disability	DISMBNXP	moderate	Biomarker	[14]
Keratolytic winter erythema	DIS2TO10	Moderate	Autosomal dominant	[15]
Movement disorder	DISOJJ2D	moderate	CausalMutation	[16]
Progressive myoclonus epilepsy	DISAMCNS	moderate	Biomarker	[17]
Autosomal recessive hypohidrotic ectodermal dysplasia	DISGAO5V	Supportive	Autosomal recessive	[18]
Meningioma	DISPT4TG	Disputed	Biomarker	[11]
Abdominal aortic aneurysm	DISD06OF	Limited	Biomarker	[19]
Nervous system disease	DISJ7GGT	Limited	Genetic Variation	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Cystatin-B (CSTB).	[21]

15 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 Cystatin-B (CSTB).	[22]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cystatin-B (CSTB).	[23]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cystatin-B (CSTB).	[24]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cystatin-B (CSTB).	[25]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cystatin-B (CSTB).	[26]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Cystatin-B (CSTB).	[27]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Cystatin-B (CSTB).	[28]
Marinol	DM70IK5	Approved	Marinol increases the expression of Cystatin-B (CSTB).	[29]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Cystatin-B (CSTB).	[30]
Coprexa	DMA0WEK	Phase 3	Coprexa decreases the expression of Cystatin-B (CSTB).	[31]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cystatin-B (CSTB).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Cystatin-B (CSTB).	[33]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Cystatin-B (CSTB).	[34]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Cystatin-B (CSTB).	[35]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Cystatin-B (CSTB).	[36]

References

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• [18] Deficiency of the human cysteine protease inhibitor cystatin M/E causes hypotrichosis and dry skin. Genet Med. 2019 Jul;21(7):1559-1567. doi: 10.1038/s41436-018-0355-3. Epub 2018 Nov 14.
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• [23] Arsenic targets Pin1 and cooperates with retinoic acid to inhibit cancer-driving pathways and tumor-initiating cells. Nat Commun. 2018 Aug 9;9(1):3069. doi: 10.1038/s41467-018-05402-2.
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