Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8T5NYL)

• DOT Name: Cytokine-inducible SH2-containing protein (CISH)
• Synonyms: CIS; CIS-1; Protein G18; Suppressor of cytokine signaling; SOCS
• Gene Name: CISH
• Related Disease:
  Adenocarcinoma
  Allergic contact dermatitis
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Bacteremia
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Carcinoma
  Cervical cancer
  Cervical carcinoma
  Clear cell renal carcinoma
  Colorectal carcinoma
  Cytomegalovirus infection
  Cytomegalovirus retinitis
  Depression
  Gastric cancer
  Glaucoma/ocular hypertension
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Herpes simplex infection
  Melanoma
  Multiple sclerosis
  Myeloproliferative neoplasm
  Osteoarthritis
  Osteosarcoma
  Precancerous condition
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Rheumatoid arthritis
  Squamous cell carcinoma
  Stomach cancer
  Thyroid gland papillary carcinoma
  Transitional cell carcinoma
  Tuberculosis
  Ulcerative colitis
  Urinary bladder cancer
  Germ cell tumor
  Hepatitis C virus infection
  Immune system disorder
  Neuromyelitis optica
  Non-insulin dependent diabetes
  Obesity
• UniProt ID: CISH_HUMAN
• Pfam ID: PF00017 ; PF07525
• Sequence:
  MVLCVQGPRPLLAVERTGQRPLWAPSLELPKPVMQPLPAGAFLEEVAEGTPAQTESEPKV
  LDPEEDLLCIAKTFSYLRESGWYWGSITASEARQHLQKMPEGTFLVRDSTHPSYLFTLSV
  KTTRGPTNVRIEYADSSFRLDSNCLSRPRILAFPDVVSLVQHYVASCTADTRSDSPDPAP
  TPALPMPKEDAPSDPALPAPPPATAVHLKLVQPFVRRSSARSLQHLCRLVINRLVADVDC
  LPLPRRMADYLRQYPFQL
• Function: SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. CIS is involved in the negative regulation of cytokines that signal through the JAK-STAT5 pathway such as erythropoietin, prolactin and interleukin 3 (IL3) receptor. Inhibits STAT5 trans-activation by suppressing its tyrosine phosphorylation. May be a substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
• Tissue Specificity: Expressed in various epithelial tissues. Abundantly expressed in liver and kidney, and to a lesser extent in lung. The tissue distribution of isoforms 1 and 1B is distinct.
• KEGG Pathway:
  JAK-STAT sig.ling pathway (hsa04630)
  Prolactin sig.ling pathway (hsa04917)
• Reactome Pathway:
  Neddylation (R-HSA-8951664)
  Growth hormone receptor signaling (R-HSA-982772)
  Interleukin-7 signaling (R-HSA-1266695)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Genetic Variation	[1]
Allergic contact dermatitis	DISFFVF9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[3]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[4]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[4]
Bacteremia	DIS6N9RZ	Strong	Genetic Variation	[5]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Carcinoma	DISH9F1N	Strong	Biomarker	[8]
Cervical cancer	DISFSHPF	Strong	Biomarker	[9]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[9]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[11]
Cytomegalovirus infection	DISCEMGC	Strong	Altered Expression	[12]
Cytomegalovirus retinitis	DIS5JC9D	Strong	Biomarker	[13]
Depression	DIS3XJ69	Strong	Biomarker	[14]
Gastric cancer	DISXGOUK	Strong	Biomarker	[15]
Glaucoma/ocular hypertension	DISLBXBY	Strong	Biomarker	[16]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[17]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[18]
Herpes simplex infection	DISL1SAV	Strong	Altered Expression	[13]
Melanoma	DIS1RRCY	Strong	Altered Expression	[19]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[20]
Myeloproliferative neoplasm	DIS5KAPA	Strong	Genetic Variation	[21]
Osteoarthritis	DIS05URM	Strong	Biomarker	[22]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[6]
Precancerous condition	DISV06FL	Strong	Biomarker	[23]
Prostate cancer	DISF190Y	Strong	Altered Expression	[24]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[24]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[10]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[25]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[26]
Stomach cancer	DISKIJSX	Strong	Biomarker	[15]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Altered Expression	[27]
Transitional cell carcinoma	DISWVVDR	Strong	Biomarker	[28]
Tuberculosis	DIS2YIMD	Strong	Altered Expression	[29]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[30]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[31]
Germ cell tumor	DIS62070	Limited	Biomarker	[32]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[33]
Immune system disorder	DISAEGPH	Limited	Biomarker	[34]
Neuromyelitis optica	DISBFGKL	Limited	Biomarker	[35]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Posttranslational Modification	[36]
Obesity	DIS47Y1K	Limited	Altered Expression	[37]

15 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 Cytokine-inducible SH2-containing protein (CISH).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cytokine-inducible SH2-containing protein (CISH).	[39]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cytokine-inducible SH2-containing protein (CISH).	[40]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cytokine-inducible SH2-containing protein (CISH).	[41]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cytokine-inducible SH2-containing protein (CISH).	[42]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Cytokine-inducible SH2-containing protein (CISH).	[43]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Cytokine-inducible SH2-containing protein (CISH).	[44]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Cytokine-inducible SH2-containing protein (CISH).	[45]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Cytokine-inducible SH2-containing protein (CISH).	[46]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Cytokine-inducible SH2-containing protein (CISH).	[41]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Cytokine-inducible SH2-containing protein (CISH).	[47]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cytokine-inducible SH2-containing protein (CISH).	[49]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Cytokine-inducible SH2-containing protein (CISH).	[50]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cytokine-inducible SH2-containing protein (CISH).	[51]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Cytokine-inducible SH2-containing protein (CISH).	[52]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Cytokine-inducible SH2-containing protein (CISH).	[48]

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