Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV88X2G)

• DOT Name: Collagen triple helix repeat-containing protein 1 (CTHRC1)
• Gene Name: CTHRC1
• Related Disease:
  Advanced cancer
  Arthritis
  B-cell neoplasm
  Carcinoma
  Cervical cancer
  Cervical carcinoma
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Endometriosis
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Gastric cancer
  Gastrointestinal stromal tumour
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Influenza
  Keloid
  Liver cirrhosis
  Lung adenocarcinoma
  Neoplasm
  Non-small-cell lung cancer
  Osteoarthritis
  Osteoporosis
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Rheumatoid arthritis
  Stomach cancer
  Systemic lupus erythematosus
  Vascular disease
  Breast cancer
  Breast carcinoma
  Metastatic malignant neoplasm
  Pulmonary fibrosis
  Adult glioblastoma
  Barrett esophagus
  Bone osteosarcoma
  Colorectal carcinoma
  Endometrial cancer
  Endometrial carcinoma
  Glioblastoma multiforme
  Melanoma
  Osteosarcoma
• UniProt ID: CTHR1_HUMAN
• Sequence:
  MRPQGPAASPQRLRGLLLLLLLQLPAPSSASEIPKGKQKAQLRQREVVDLYNGMCLQGPA
  GVPGRDGSPGANGIPGTPGIPGRDGFKGEKGECLRESFEESWTPNYKQCSWSSLNYGIDL
  GKIAECTFTKMRSNSALRVLFSGSLRLKCRNACCQRWYFTFNGAECSGPLPIEAIIYLDQ
  GSPEMNSTINIHRTSSVEGLCEGIGAGLVDVAIWVGTCSDYPKGDASTGWNSVSRIIIEE
  LPK
• Function: May act as a negative regulator of collagen matrix deposition.
• Tissue Specificity: Isoform 1 is expressed in calcified atherosclerotic plaque and chondrocyte-like cells.

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]
Arthritis	DIST1YEL	Strong	Biomarker	[2]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[3]
Carcinoma	DISH9F1N	Strong	Altered Expression	[4]
Cervical cancer	DISFSHPF	Strong	Biomarker	[5]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[6]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[7]
Colon cancer	DISVC52G	Strong	Altered Expression	[8]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[8]
Endometriosis	DISX1AG8	Strong	Biomarker	[9]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[10]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[11]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[12]
Gastrointestinal stromal tumour	DIS6TJYS	Strong	Biomarker	[13]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[15]
Influenza	DIS3PNU3	Strong	Altered Expression	[16]
Keloid	DISV09JY	Strong	Altered Expression	[17]
Liver cirrhosis	DIS4G1GX	Strong	Altered Expression	[18]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[19]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[6]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[20]
Osteoarthritis	DIS05URM	Strong	Biomarker	[2]
Osteoporosis	DISF2JE0	Strong	Biomarker	[21]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[10]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[10]
Pancreatic cancer	DISJC981	Strong	Biomarker	[22]
Prostate cancer	DISF190Y	Strong	Biomarker	[23]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[23]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[7]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[2]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[12]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[24]
Vascular disease	DISVS67S	Strong	Biomarker	[25]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[26]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[26]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[1]
Pulmonary fibrosis	DISQKVLA	moderate	Biomarker	[27]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[28]
Barrett esophagus	DIS416Y7	Limited	Autosomal dominant	[29]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[30]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[31]
Endometrial cancer	DISW0LMR	Limited	Biomarker	[1]
Endometrial carcinoma	DISXR5CY	Limited	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[28]
Melanoma	DIS1RRCY	Limited	Biomarker	[32]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[30]

18 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 Collagen triple helix repeat-containing protein 1 (CTHRC1).	[33]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Collagen triple helix repeat-containing protein 1 (CTHRC1).	[34]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Collagen triple helix repeat-containing protein 1 (CTHRC1).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Collagen triple helix repeat-containing protein 1 (CTHRC1).	[36]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Collagen triple helix repeat-containing protein 1 (CTHRC1).	[37]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Collagen triple helix repeat-containing protein 1 (CTHRC1).	[38]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Collagen triple helix repeat-containing protein 1 (CTHRC1).	[39]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Collagen triple helix repeat-containing protein 1 (CTHRC1).	[40]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Collagen triple helix repeat-containing protein 1 (CTHRC1).	[41]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Collagen triple helix repeat-containing protein 1 (CTHRC1).	[42]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Collagen triple helix repeat-containing protein 1 (CTHRC1).	[38]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Collagen triple helix repeat-containing protein 1 (CTHRC1).	[43]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Collagen triple helix repeat-containing protein 1 (CTHRC1).	[41]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Collagen triple helix repeat-containing protein 1 (CTHRC1).	[44]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Collagen triple helix repeat-containing protein 1 (CTHRC1).	[41]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Collagen triple helix repeat-containing protein 1 (CTHRC1).	[46]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Collagen triple helix repeat-containing protein 1 (CTHRC1).	[47]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Collagen triple helix repeat-containing protein 1 (CTHRC1).	[48]

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 increases the methylation of Collagen triple helix repeat-containing protein 1 (CTHRC1).	[45]

References

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• [2] CTHRC1: A New Candidate Biomarker for Improved Rheumatoid Arthritis Diagnosis.Front Immunol. 2019 Jun 12;10:1353. doi: 10.3389/fimmu.2019.01353. eCollection 2019.
• [3] CTHRC1 mediates IL?induced apoptosis in chondrocytes via JNK1/2 signaling.Int J Mol Med. 2018 Apr;41(4):2270-2278. doi: 10.3892/ijmm.2018.3403. Epub 2018 Jan 18.
• [4] Cthrc1 overexpression is an independent prognostic marker in gastric cancer.Hum Pathol. 2014 May;45(5):1031-8. doi: 10.1016/j.humpath.2013.12.020. Epub 2014 Jan 21.
• [5] Inhibition of CTHRC-1 by its specific monoclonal antibody attenuates cervical cancer cell metastasis.Biomed Pharmacother. 2019 Feb;110:758-763. doi: 10.1016/j.biopha.2018.12.017. Epub 2018 Dec 13.
• [6] CTHRC1 overexpression promotes cervical carcinoma progression by activating the Wnt/PCP signaling pathway.Oncol Rep. 2019 Mar;41(3):1531-1538. doi: 10.3892/or.2019.6963. Epub 2019 Jan 10.
• [7] Knockdown of Collagen Triple Helix Repeat Containing-1 Inhibits the Proliferation and Epithelial-to-Mesenchymal Transition in Renal Cell Carcinoma Cells.Oncol Res. 2016 Oct 27;24(6):477-485. doi: 10.3727/096504016X14685034103716.
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• [17] Increased Cthrc1 Activates Normal Fibroblasts and Suppresses Keloid Fibroblasts by Inhibiting TGF-/Smad Signal Pathway and Modulating YAP Subcellular Location.Curr Med Sci. 2018 Oct;38(5):894-902. doi: 10.1007/s11596-018-1959-1. Epub 2018 Oct 20.
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• [19] High CTHRC1 expression may be closely associated with angiogenesis and indicates poor prognosis in lung adenocarcinoma patients.Cancer Cell Int. 2019 Nov 29;19:318. doi: 10.1186/s12935-019-1041-5. eCollection 2019.
• [20] CTHRC1 induces non-small cell lung cancer (NSCLC) invasion through upregulating MMP-7/MMP-9.BMC Cancer. 2018 Apr 10;18(1):400. doi: 10.1186/s12885-018-4317-6.
• [21] Extracellular vesicles from human urine-derived stem cells prevent osteoporosis by transferring CTHRC1 and OPG.Bone Res. 2019 Jun 26;7:18. doi: 10.1038/s41413-019-0056-9. eCollection 2019.
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• [23] CTHRC1 and PD?/PDL1 expression predicts tumor recurrence in prostate cancer.Mol Med Rep. 2019 Nov;20(5):4244-4252. doi: 10.3892/mmr.2019.10690. Epub 2019 Sep 19.
• [24] Collagen triple helix repeat containing-1: a novel biomarker associated with disease activity in Systemic lupus erythematosus.Lupus. 2018 Nov;27(13):2076-2085. doi: 10.1177/0961203318804877. Epub 2018 Oct 18.
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• [31] MicroRNA-155 acts as a tumor suppressor in colorectal cancer by targeting CTHRC1 in vitro.Oncol Lett. 2018 Apr;15(4):5561-5568. doi: 10.3892/ol.2018.8069. Epub 2018 Feb 16.
• [32] Gene expression analyses of primary melanomas reveal CTHRC1 as an important player in melanoma progression.Oncotarget. 2016 Mar 22;7(12):15065-92. doi: 10.18632/oncotarget.7604.
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• [38] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
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