Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT788NC8)

• DOT Name: Neural proliferation differentiation and control protein 1 (NPDC1)
• Synonyms: NPDC-1
• Gene Name: NPDC1
• Related Disease:
  Parkinson disease
  Acromegaly
  Colon cancer
  Colon carcinoma
  Skin cancer
  Sleep disorder
  Alcohol dependence
  Neuroblastoma
• UniProt ID: NPDC1_HUMAN
• Pfam ID: PF06809
• Sequence:
  MATPLPPPSPRHLRLLRLLLSGLVLGAALRGAAAGHPDVAACPGSLDCALKRRARCPPGA
  HACGPCLQPFQEDQQGLCVPRMRRPPGGGRPQPRLEDEIDFLAQELARKESGHSTPPLPK
  DRQRLPEPATLGFSARGQGLELGLPSTPGTPTPTPHTSLGSPVSSDPVHMSPLEPRGGQG
  DGLALVLILAFCVAGAAALSVASLCWCRLQREIRLTQKADYATAKAPGSPAAPRISPGDQ
  RLAQSAEMYHYQHQRQQMLCLERHKEPPKELDTASSDEENEDGDFTVYECPGLAPTGEME
  VRNPLFDHAALSAPLPAPSSPPALP
• Function: Suppresses oncogenic transformation in neural and non-neural cells and down-regulates neural cell proliferation. Might be involved in transcriptional regulation.
• Tissue Specificity: Strongly expressed in adult brain; especially in hippocampus, frontal lobe and temporal lobe.
• Reactome Pathway: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Parkinson disease	DISQVHKL	Definitive	Biomarker	[1]
Acromegaly	DISCC73U	Strong	Biomarker	[2]
Colon cancer	DISVC52G	Strong	Biomarker	[3]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[3]
Skin cancer	DISTM18U	Strong	Biomarker	[4]
Sleep disorder	DIS3JP1U	Strong	Biomarker	[5]
Alcohol dependence	DIS4ZSCO	moderate	Biomarker	[6]
Neuroblastoma	DISVZBI4	Disputed	Biomarker	[7]

2 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 Neural proliferation differentiation and control protein 1 (NPDC1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Neural proliferation differentiation and control protein 1 (NPDC1).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Neural proliferation differentiation and control protein 1 (NPDC1).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Neural proliferation differentiation and control protein 1 (NPDC1).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Neural proliferation differentiation and control protein 1 (NPDC1).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Neural proliferation differentiation and control protein 1 (NPDC1).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Neural proliferation differentiation and control protein 1 (NPDC1).	[13]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Neural proliferation differentiation and control protein 1 (NPDC1).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Neural proliferation differentiation and control protein 1 (NPDC1).	[16]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Neural proliferation differentiation and control protein 1 (NPDC1).	[17]

References

• [1] Inhibition of microRNA-505 suppressed MPP+?induced cytotoxicity of SHSY5Y cells in an in vitro Parkinson's disease model.Eur J Pharmacol. 2018 Sep 15;835:11-18. doi: 10.1016/j.ejphar.2018.07.023. Epub 2018 Jul 17.
• [2] The efficacy of medical treatment in patients with acromegaly in clinical practice.Endocr J. 2018 Jan 30;65(1):33-41. doi: 10.1507/endocrj.EJ17-0125. Epub 2017 Sep 20.
• [3] High efficiency reconstitution of a human-mouse chimeric Fab of CAb-1 antibody specific to human colon cancer.Scand J Immunol. 2008 Jul;68(1):12-21. doi: 10.1111/j.1365-3083.2008.02087.x. Epub 2008 May 13.
• [4] Design, Synthesis, and Biological Evaluation of Polyaminocarboxylate Ligand-Based Theranostic Conjugates for Antibody-Targeted Cancer Therapy and Near-Infrared Optical Imaging.ChemMedChem. 2018 Dec 20;13(24):2606-2617. doi: 10.1002/cmdc.201800598. Epub 2018 Nov 26.
• [5] Factors Associated with Potassium-Competitive Acid Blocker Non-Response in Patients with Proton Pump Inhibitor-Refractory Gastroesophageal Reflux Disease.Digestion. 2017;95(4):281-287. doi: 10.1159/000475658. Epub 2017 May 13.
• [6] Integrative epigenetic profiling analysis identifies DNA methylation changes associated with chronic alcohol consumption.Comput Biol Med. 2015 Sep;64:299-306. doi: 10.1016/j.compbiomed.2014.12.003. Epub 2014 Dec 11.
• [7] Polypyrrole-coated cellulose nanofibers: influence of orientation, coverage and electrical stimulation on SH-SY5Y behavior.J Mater Chem B. 2019 Nov 14;7(42):6500-6507. doi: 10.1039/c9tb01300h. Epub 2019 Oct 2.
• [8] 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.
• [9] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [10] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [13] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [14] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [15] 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.
• [16] 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.
• [17] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.