Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUEH5X5)

• DOT Name: Cementoblastoma-derived protein 1 (CEMP1)
• Synonyms: Cementum protein 1; Cementum protein 23; CP-23
• Gene Name: CEMP1
• Related Disease:
  Cryptosporidium infection
  Advanced cancer
  leukaemia
  Leukemia
  Lung cancer
  Lung carcinoma
  Chronic pancreatitis
• UniProt ID: CEMP1_HUMAN
• PDB ID: 7TB9
• Sequence:
  MGTSSTDSQQAGHRRCSTSNTSAENLTCLSLPGSPGKTAPLPGPAQAGAGQPLPKGCAAV
  KAEVGIPAPHTSQEVRIHIRRLLSWAAPGACGLRSTPCALPQALPQARPCPGRWFFPGCS
  LPTGGAQTILSLWTWRHFLNWALQQREENSGRARRVPPVPRTAPVSKGEGSHPPQNSNGE
  KVKTITPDVGLHQSLTSDPTVAVLRAKRAPEAHPPRSCSGSLTARVCHMGVCQGQGDTED
  GRMTLMG
• Function: May play a role in development of the periodontium which surrounds and supports the teeth by promoting the differentiation of multi-potent cells from the periodontal ligament into cementoblasts to form the cementum. Binds hydroxyapatite and may promote the biomineralization of the cementum. Also promotes cell proliferation.
• Tissue Specificity: Expressed by cementoblasts, a subpopulation of periodontal ligament cells and cells located around vessels in periodontium (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cryptosporidium infection	DISLBTU2	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[2]
leukaemia	DISS7D1V	moderate	Altered Expression	[2]
Leukemia	DISNAKFL	moderate	Altered Expression	[2]
Lung cancer	DISCM4YA	moderate	Altered Expression	[2]
Lung carcinoma	DISTR26C	moderate	Altered Expression	[2]
Chronic pancreatitis	DISBUOMJ	Limited	Biomarker	[3]

3 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 Cementoblastoma-derived protein 1 (CEMP1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cementoblastoma-derived protein 1 (CEMP1).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Cementoblastoma-derived protein 1 (CEMP1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Cementoblastoma-derived protein 1 (CEMP1).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Cementoblastoma-derived protein 1 (CEMP1).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cementoblastoma-derived protein 1 (CEMP1).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Cementoblastoma-derived protein 1 (CEMP1).	[10]

References

• [1] Fecal Immunoglobulin A Against a Sporozoite Antigen at 12 Months Is Associated With Delayed Time to Subsequent Cryptosporidiosis in Urban Bangladesh: A Prospective Cohort Study.Clin Infect Dis. 2020 Jan 2;70(2):323-326. doi: 10.1093/cid/ciz430.
• [2] CEMP1 Induces Transformation in Human Gingival Fibroblasts.PLoS One. 2015 May 26;10(5):e0127286. doi: 10.1371/journal.pone.0127286. eCollection 2015.
• [3] Tumor angiogenesis in chronic pancreatitis and pancreatic adenocarcinoma: impact of K-ras mutations.Pancreas. 2000 Apr;20(3):248-55. doi: 10.1097/00006676-200004000-00005.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [7] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [8] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [9] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.