Details of Drug Off-Target (DOT)

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

• DOT Name: Cystatin-F (CST7)
• Synonyms: Cystatin-7; Cystatin-like metastasis-associated protein; CMAP; Leukocystatin
• Gene Name: CST7
• Related Disease:
  Hepatocellular carcinoma
  Aicardi-Goutieres syndrome
  Alzheimer disease
  Amyloidosis
  Chronic inflammatory demyelinating polyneuropathy
  Creutzfeldt Jacob disease
  Multiple sclerosis
  Neoplasm
  Non-insulin dependent diabetes
  Peripheral neuropathy
  Prion disease
  Spinal muscular atrophy, type II
  Amyotrophic lateral sclerosis
  Type-1/2 diabetes
  Advanced cancer
  Colorectal carcinoma
  Gastric cancer
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  Matthew-Wood syndrome
  Pancreatic ductal carcinoma
• UniProt ID: CYTF_HUMAN
• PDB ID: 2CH9
• Pfam ID: PF00031
• Sequence:
  MRAAGTLLAFCCLVLSTTGGPSPDTCSQDLNSRVKPGFPKTIKTNDPGVLQAARYSVEKF
  NNCTNDMFLFKESRITRALVQIVKGLKYMLEVEIGRTTCKKNQHLRLDDCDFQTNHTLKQ
  TLSCYSEVWVVPWLQHFEVPVLRCH
• Function: Inhibits papain and cathepsin L but with affinities lower than other cystatins. May play a role in immune regulation through inhibition of a unique target in the hematopoietic system.
• Tissue Specificity: Primarily expressed in peripheral blood cells and spleen.

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Altered Expression	[1]
Aicardi-Goutieres syndrome	DIS1NH4X	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[3]
Amyloidosis	DISHTAI2	Strong	Genetic Variation	[4]
Chronic inflammatory demyelinating polyneuropathy	DISNGBLD	Strong	Genetic Variation	[5]
Creutzfeldt Jacob disease	DISCB6RX	Strong	Altered Expression	[3]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[7]
Peripheral neuropathy	DIS7KN5G	Strong	Biomarker	[7]
Prion disease	DISOUMB0	Strong	Biomarker	[3]
Spinal muscular atrophy, type II	DIS3GNQ4	Strong	Biomarker	[8]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Biomarker	[9]
Type-1/2 diabetes	DISIUHAP	moderate	Biomarker	[10]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[11]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[12]
Gastric cancer	DISXGOUK	Limited	Biomarker	[13]
Gastric neoplasm	DISOKN4Y	Limited	Biomarker	[13]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Limited	Biomarker	[13]
Matthew-Wood syndrome	DISA7HR7	Limited	Altered Expression	[14]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Biomarker	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cystatin-F (CST7).	[15]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cystatin-F (CST7).	[16]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Cystatin-F (CST7).	[17]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Cystatin-F (CST7).	[13]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Cystatin-F (CST7).	[19]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Cystatin-F (CST7).	[20]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Cystatin-F (CST7).	[21]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of Cystatin-F (CST7).	[22]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Cystatin-F (CST7).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Cystatin-F (CST7).	[24]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cystatin-F (CST7).	[25]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Cystatin-F (CST7).	[26]

References

• [1] Investigation of the clinical significance and prospective molecular mechanisms of cystatin genes in patients with hepatitis B virusrelated hepatocellular carcinoma.Oncol Rep. 2019 Jul;42(1):189-201. doi: 10.3892/or.2019.7154. Epub 2019 May 9.
• [2] The Aicardi-Goutires syndrome. Molecular and clinical features of RNAse deficiency and microRNA overload.Mutat Res. 2011 Dec 1;717(1-2):99-108. doi: 10.1016/j.mrfmmm.2011.03.018. Epub 2011 Apr 15.
• [3] Cystatin F is a biomarker of prion pathogenesis in mice.PLoS One. 2017 Feb 8;12(2):e0171923. doi: 10.1371/journal.pone.0171923. eCollection 2017.
• [4] Integrative approach to sporadic Alzheimer's disease:deficiency of TYROBPin cerebral A amyloidosis mouse normalizes clinical phenotype and complement subnetwork molecular pathology without reducing A burden.Mol Psychiatry. 2019 Mar;24(3):431-446. doi: 10.1038/s41380-018-0255-6. Epub 2018 Oct 3.
• [5] Blink R1 latency utility in diagnosis and treatment assessment of polyradiculoneuropathy-organomegaly-endocrinopathy-monoclonal protein-skin changes and chronic inflammatory demyelinating polyradiculoneuropathy.Muscle Nerve. 2018 Jan;57(1):E8-E13. doi: 10.1002/mus.25731. Epub 2017 Jul 7.
• [6] Cathepsin C modulates myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis.J Neurochem. 2019 Feb;148(3):413-425. doi: 10.1111/jnc.14581. Epub 2018 Dec 3.
• [7] The role of dietary non-heme iron load and peripheral nerve inflammation in the development of peripheral neuropathy (PN) in obese non-diabetic leptin-deficient ob/ob mice.Neurol Res. 2019 Apr;41(4):341-353. doi: 10.1080/01616412.2018.1564191. Epub 2019 Jan 13.
• [8] Peripheral nerve abnormalities in pediatric patients with spinal muscular atrophy.Brain Dev. 2013 Feb;35(2):165-71. doi: 10.1016/j.braindev.2012.03.009. Epub 2012 Apr 17.
• [9] The split hand in amyotrophic lateral sclerosis: a possible role for the neuromuscular junction.Amyotroph Lateral Scler Frontotemporal Degener. 2019 Aug;20(5-6):368-375. doi: 10.1080/21678421.2019.1606245. Epub 2019 May 6.
• [10] Influence of comorbidities on the phenotype of patients affected by Charcot-Marie-Tooth neuropathy type 1A.Neuromuscul Disord. 2013 Nov;23(11):902-6. doi: 10.1016/j.nmd.2013.07.002. Epub 2013 Jul 23.
• [11] Identifying prognostic signature in ovarian cancer using DirGenerank.Oncotarget. 2017 Jul 11;8(28):46398-46413. doi: 10.18632/oncotarget.18189.
• [12] Analysis of the K-ras/B-raf/Erk signal cascade, p53 and CMAP as markers for tumor progression in colorectal cancer patients.Oncol Rep. 2008 Jul;20(1):3-11.
• [13] Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 2006 Jan;97(1):64-71.
• [14] Cystatin F as a key family 2 cystatin subunit and prognostic biomarker for earlystage pancreatic ductal adenocarcinoma.Oncol Rep. 2019 Jul;42(1):79-90. doi: 10.3892/or.2019.7135. Epub 2019 Apr 24.
• [15] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [16] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [17] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [18] Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 2006 Jan;97(1):64-71.
• [19] Dissecting progressive stages of 5-fluorouracil resistance in vitro using RNA expression profiling. Int J Cancer. 2004 Nov 1;112(2):200-12. doi: 10.1002/ijc.20401.
• [20] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [21] Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors. Leuk Res. 2007 Nov;31(11):1511-20.
• [22] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [23] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [24] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [25] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [26] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.