Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYJ0LMA)

• DOT Name: C-type natriuretic peptide (NPPC)
• Gene Name: NPPC
• Related Disease: Short stature with nonspecific skeletal abnormalities
• UniProt ID: ANFC_HUMAN
• PDB ID: 1JDP
• Pfam ID: PF00212
• Sequence:
  MHLSQLLACALLLTLLSLRPSEAKPGAPPKVPRTPPAEELAEPQAAGGGQKKGDKAPGGG
  GANLKGDRSRLLRDLRVDTKSRAAWARLLQEHPNARKYKGANKKGLSKGCFGLKLDRIGS
  MSGLGC
• Function: [CNP-22]: Hormone which plays a role in endochondral ossification through regulation of cartilaginous growth plate chondrocytes proliferation and differentiation. May also be vasoactive and natriuretic. Acts by specifically binding and stimulating NPR2 to produce cGMP. Binds the clearance receptor NPR3.
• Tissue Specificity: .In the kidney, predominantly expressed in the distal tubular cells (at protein level).
• KEGG Pathway:
  cGMP-PKG sig.ling pathway (hsa04022)
  Vascular smooth muscle contraction (hsa04270)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway: Physiological factors (R-HSA-5578768)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Short stature with nonspecific skeletal abnormalities	DISRNBJZ	Limited	Autosomal dominant	[1]

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 C-type natriuretic peptide (NPPC).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of C-type natriuretic peptide (NPPC).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of C-type natriuretic peptide (NPPC).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of C-type natriuretic peptide (NPPC).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of C-type natriuretic peptide (NPPC).	[5]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of C-type natriuretic peptide (NPPC).	[5]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of C-type natriuretic peptide (NPPC).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of C-type natriuretic peptide (NPPC).	[7]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of C-type natriuretic peptide (NPPC).	[8]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of C-type natriuretic peptide (NPPC).	[9]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of C-type natriuretic peptide (NPPC).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of C-type natriuretic peptide (NPPC).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of C-type natriuretic peptide (NPPC).	[12]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of C-type natriuretic peptide (NPPC).	[13]

References

• [1] Mutations in C-natriuretic peptide (NPPC): a novel cause of autosomal dominant short stature. Genet Med. 2018 Jan;20(1):91-97. doi: 10.1038/gim.2017.66. Epub 2017 Jun 28.
• [2] 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.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [5] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [6] Genistein disrupts glucocorticoid receptor signaling in human uterine endometrial Ishikawa cells. Environ Health Perspect. 2015 Jan;123(1):80-7. doi: 10.1289/ehp.1408437. Epub 2014 Aug 19.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [9] Activation of SIRT1 by resveratrol induces KLF2 expression conferring an endothelial vasoprotective phenotype. Cardiovasc Res. 2010 Feb 1;85(3):514-9. doi: 10.1093/cvr/cvp337. Epub 2009 Oct 8.
• [10] 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.
• [11] The effect of bisphenol a exposure onto endothelial and decidualized stromal cells on regulation of the invasion ability of trophoblastic spheroids in in?vitro co-culture model. Biochem Biophys Res Commun. 2019 Aug 20;516(2):506-514. doi: 10.1016/j.bbrc.2019.06.066. Epub 2019 Jun 21.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.