Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHND8EL)

DOT Name	Leukocyte cell-derived chemotaxin 1 (CNMD)
Synonyms	Chondromodulin
Gene Name	CNMD
Related Disease	Breast cancer ( ) Breast carcinoma ( ) Heart valve disorder ( ) Adult respiratory distress syndrome ( ) Advanced cancer ( ) Carcinoma of esophagus ( ) Dementia ( ) Esophageal cancer ( ) Esophageal squamous cell carcinoma ( ) Ewing sarcoma ( ) Gastric adenocarcinoma ( ) Gastric cancer ( ) Hydatidiform mole ( ) Hydatidiform mole, recurrent, 1 ( ) Malignant soft tissue neoplasm ( ) Multiple endocrine neoplasia type 2B ( ) Neoplasm of esophagus ( ) Osteoarthritis ( ) Pityriasis rubra pilaris ( ) Sarcoma ( ) Stomach cancer ( ) Bacterial endocarditis ( ) Infective endocarditis ( ) Bone osteosarcoma ( ) Colon adenocarcinoma ( ) Congenital alveolar dysplasia ( ) Epithelial ovarian cancer ( ) Neuroblastoma ( ) Osteosarcoma ( ) Ovarian cancer ( ) Ovarian neoplasm ( )
UniProt ID	CNMD_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF04089
Sequence	MTENSDKVPIALVGPDDVEFCSPPAYATLTVKPSSPARLLKVGAVVLISGAVLLLFGAIG AFYFWKGSDSHIYNVHYTMSINGKLQDGSMEIDAGNNLETFKMGSGAEEAIAVNDFQNGI TGIRFAGGEKCYIKAQVKARIPEVGAVTKQSISSKLEGKIMPVKYEENSLIWVAVDQPVK DNSFLSSKVLELCGDLPIFWLKPTYPKEIQRERREVVRKIVPTTTKRPHSGPRSNPGAGR LNNETRPSVQEDSQAFNPDNPYHQQEGESMTFDPRLDHEGICCIECRRSYTHCQKICEPL GGYYPWPYNYQGCRSACRVIMPCSWWVARILGMV
Function	Bifunctional growth regulator that stimulates the growth of cultured chondrocytes in the presence of basic fibroblast growth factor (FGF) but inhibits the growth of cultured vascular endothelial cells. May contribute to the rapid growth of cartilage and vascular invasion prior to the replacement of cartilage by bone during endochondral bone development. Inhibits in vitro tube formation and mobilization of endothelial cells. Plays a role as antiangiogenic factor in cardiac valves to suppress neovascularization.
Tissue Specificity	Detected in cartilage and cardiac valves (at protein level). Detected in the laminae fibrosa, spongiosa and ventricularis layers of normal cardiac valves (at protein level). Expression is decreased cardiac valves of patients with valvular heart disease (at protein level). Weakly expressed in chondrosarcoma.

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Breast cancer	DIS7DPX1	Definitive	Biomarker	[1]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]
Heart valve disorder	DIS84O7T	Definitive	Biomarker	[2]
Adult respiratory distress syndrome	DISIJV47	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[4]
Dementia	DISXL1WY	Strong	Biomarker	[5]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[4]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[4]
Ewing sarcoma	DISQYLV3	Strong	Biomarker	[6]
Gastric adenocarcinoma	DISWWLTC	Strong	Biomarker	[7]
Gastric cancer	DISXGOUK	Strong	Biomarker	[7]
Hydatidiform mole	DISKNP7O	Strong	Biomarker	[8]
Hydatidiform mole, recurrent, 1	DISXUJWE	Strong	Biomarker	[8]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[9]
Multiple endocrine neoplasia type 2B	DIS6FT6I	Strong	Altered Expression	[10]
Neoplasm of esophagus	DISOLKAQ	Strong	Altered Expression	[4]
Osteoarthritis	DIS05URM	Strong	Biomarker	[11]
Pityriasis rubra pilaris	DISVC72D	Strong	Biomarker	[12]
Sarcoma	DISZDG3U	Strong	Biomarker	[9]
Stomach cancer	DISKIJSX	Strong	Biomarker	[7]
Bacterial endocarditis	DIS920N0	moderate	Biomarker	[11]
Infective endocarditis	DIS88NSA	moderate	Biomarker	[11]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[13]
Colon adenocarcinoma	DISDRE0J	Limited	Biomarker	[14]
Congenital alveolar dysplasia	DIS1IYUN	Limited	Biomarker	[3]
Epithelial ovarian cancer	DIS56MH2	Limited	Biomarker	[15]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[16]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[13]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[15]
Ovarian neoplasm	DISEAFTY	Limited	Biomarker	[15]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Leukocyte cell-derived chemotaxin 1 (CNMD).	[17]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Leukocyte cell-derived chemotaxin 1 (CNMD).	[18]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Leukocyte cell-derived chemotaxin 1 (CNMD).	[19]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Leukocyte cell-derived chemotaxin 1 (CNMD).	[20]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Leukocyte cell-derived chemotaxin 1 (CNMD).	[21]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Leukocyte cell-derived chemotaxin 1 (CNMD).	[22]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Leukocyte cell-derived chemotaxin 1 (CNMD).	[23]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Leukocyte cell-derived chemotaxin 1 (CNMD).	[21]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Leukocyte cell-derived chemotaxin 1 (CNMD).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Leukocyte cell-derived chemotaxin 1 (CNMD).	[24]
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⏷ Show the Full List of 10 Drug(s)

References

1	CHM-1, a novel microtubule-destabilizing agent exhibits antitumor activity via inducing the expression of SIRT2 in human breast cancer cells.Chem Biol Interact. 2018 Jun 1;289:98-108. doi: 10.1016/j.cbi.2018.04.007. Epub 2018 Apr 18.
2	Chondromodulin-I maintains cardiac valvular function by preventing angiogenesis.Nat Med. 2006 Oct;12(10):1151-9. doi: 10.1038/nm1476. Epub 2006 Sep 17.
3	BRICHOS domain associated with lung fibrosis, dementia and cancer--a chaperone that prevents amyloid fibril formation?.FEBS J. 2011 Oct;278(20):3893-904. doi: 10.1111/j.1742-4658.2011.08209.x. Epub 2011 Jul 5.
4	Chondromodulin-1 and vascular endothelial growth factor-A expression in esophageal squamous cell carcinoma: accelerator and brake theory for angiogenesis at the early stage of cancer progression.Esophagus. 2020 Apr;17(2):159-167. doi: 10.1007/s10388-019-00695-8. Epub 2019 Oct 8.
5	BRICHOS: a conserved domain in proteins associated with dementia, respiratory distress and cancer.Trends Biochem Sci. 2002 Jul;27(7):329-32. doi: 10.1016/s0968-0004(02)02134-5.
6	The endochondral bone protein CHM1 sustains an undifferentiated, invasive phenotype, promoting lung metastasis in Ewing sarcoma.Mol Oncol. 2017 Sep;11(9):1288-1301. doi: 10.1002/1878-0261.12057. Epub 2017 Aug 21.
7	Chondromodulin-1 functions as a tumor suppressor in gastric adenocarcinoma.Int J Oncol. 2015 Sep;47(3):941-50. doi: 10.3892/ijo.2015.3081. Epub 2015 Jul 13.
8	HySA: a Hybrid Structural variant Assembly approach using next-generation and single-molecule sequencing technologies.Genome Res. 2017 May;27(5):793-800. doi: 10.1101/gr.214767.116. Epub 2017 Jan 19.
9	Novel quinolone CHM-1 induces apoptosis and inhibits metastasis in a human osterogenic sarcoma cell line.J Orthop Res. 2009 Dec;27(12):1637-44. doi: 10.1002/jor.20937.
10	Expression profiles provide insights into early malignant potential and skeletal abnormalities in multiple endocrine neoplasia type 2B syndrome tumors.Cancer Res. 2004 Jun 1;64(11):3907-13. doi: 10.1158/0008-5472.CAN-03-3801.
11	Chondromodulin-1 in health, osteoarthritis, cancer, and heart disease.Cell Mol Life Sci. 2019 Nov;76(22):4493-4502. doi: 10.1007/s00018-019-03225-y. Epub 2019 Jul 17.
12	Platelet-rich plasma induces post-natal maturation of immature articular cartilage and correlates with LOXL1 activation.Sci Rep. 2017 Jun 16;7(1):3699. doi: 10.1038/s41598-017-02297-9.
13	ChondromodulinI suppresses tumorigenesis of human osteosarcoma cells.Mol Med Rep. 2017 Dec;16(6):8542-8548. doi: 10.3892/mmr.2017.7629. Epub 2017 Sep 26.
14	Specific loss of chondromodulin-I gene expression in chondrosarcoma and the suppression of tumor angiogenesis and growth by its recombinant protein in vivo.FEBS Lett. 1999 Sep 24;458(3):436-40. doi: 10.1016/s0014-5793(99)01201-6.
15	CHM-1 induces apoptosis via p38-mediated upregulation of DR5 expression in human ovarian cancer SKOV3 cells.Eur J Pharmacol. 2011 Nov 16;670(1):96-104. doi: 10.1016/j.ejphar.2011.08.006. Epub 2011 Sep 3.
16	Dual Roles of Ascidian Chondromodulin-1: Promoting Cell Proliferation Whilst Suppressing the Growth of Tumor Cells.Mar Drugs. 2018 Feb 11;16(2):59. doi: 10.3390/md16020059.
17	Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
18	Angiogenic potential of 3-nitro-4-hydroxy benzene arsonic acid (roxarsone). Environ Health Perspect. 2008 Apr;116(4):520-3.
19	Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
20	Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
21	A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
22	Benzene metabolite hydroquinone up-regulates chondromodulin-I and inhibits tube formation in human bone marrow endothelial cells. Mol Pharmacol. 2009 Sep;76(3):579-87. doi: 10.1124/mol.109.057323. Epub 2009 Jun 12.
23	Evaluation of developmental toxicity using undifferentiated human embryonic stem cells. J Appl Toxicol. 2015 Feb;35(2):205-18.
24	From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.