Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ11LHB)

• DOT Name: Calcitonin (CALCA)
• Gene Name: CALCA
• UniProt ID: CALC_HUMAN
• PDB ID: 2JXZ; 7TYH; 7TYO
• Pfam ID: PF00214
• Sequence:
  MGFQKFSPFLALSILVLLQAGSLHAAPFRSALESSPADPATLSEDEARLLLAALVQDYVQ
  MKASELEQEQEREGSSLDSPRSKRCGNLSTCMLGTYTQDFNKFHTFPQTAIGVGAPGKKR
  DMSSDLERDHRPHVSMPQNAN
• Function: Calcitonin causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones.; Katacalcin is a potent plasma calcium-lowering peptide.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Vascular smooth muscle contraction (hsa04270)
• Reactome Pathway:
  Calcitonin-like ligand receptors (R-HSA-419812)
  Amyloid fiber formation (R-HSA-977225)
  G alpha (s) signalling events (R-HSA-418555)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Dexamethasone	DMMWZET	Approved	Calcitonin (CALCA) decreases the response to substance of Dexamethasone.	[17]
Etoposide	DMNH3PG	Approved	Calcitonin (CALCA) decreases the response to substance of Etoposide.	[17]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
[3H]cAMP	DMZRQU7	Investigative	Calcitonin (CALCA) increases the abundance of [3H]cAMP.	[18]

18 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 Calcitonin (CALCA).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Calcitonin (CALCA).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Calcitonin (CALCA).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Calcitonin (CALCA).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Calcitonin (CALCA).	[5]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Calcitonin (CALCA).	[5]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Calcitonin (CALCA).	[6]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Calcitonin (CALCA).	[8]
Fructose	DM43AN2	Approved	Fructose increases the expression of Calcitonin (CALCA).	[9]
Ranitidine	DM0GUSX	Approved	Ranitidine increases the expression of Calcitonin (CALCA).	[10]
Nizatidine	DMGFV3Z	Approved	Nizatidine increases the expression of Calcitonin (CALCA).	[10]
Glyceryl trinitrate	DMF72W3	Phase 4	Glyceryl trinitrate affects the expression of Calcitonin (CALCA).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Calcitonin (CALCA).	[5]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Calcitonin (CALCA).	[12]
PMID26560530-Compound-25	DMZ43OM	Patented	PMID26560530-Compound-25 increases the expression of Calcitonin (CALCA).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Calcitonin (CALCA).	[15]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Calcitonin (CALCA).	[9]
tryptanthrin	DMTRYCI	Investigative	tryptanthrin increases the expression of Calcitonin (CALCA).	[16]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the methylation of Calcitonin (CALCA).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Calcitonin (CALCA).	[13]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [2] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [7] Intriguing response to azacitidine in a patient with juvenile myelomonocytic leukemia and monosomy 7. Blood. 2009 Mar 19;113(12):2867-8. doi: 10.1182/blood-2008-12-195693.
• [8] Transient receptor potential vanilloid 1-mediated expression and secretion of endothelial cell-derived calcitonin gene-related peptide. Regul Pept. 2008 Oct 9;150(1-3):66-72. doi: 10.1016/j.regpep.2008.05.007. Epub 2008 Jun 3.
• [9] Non-nutritional sweeteners effects on endothelial vascular function. Toxicol In Vitro. 2020 Feb;62:104694. doi: 10.1016/j.tiv.2019.104694. Epub 2019 Oct 23.
• [10] Effects of histamine H(2)-receptor antagonists on human plasma levels of calcitonin gene-related peptide, substance P and vasoactive intestinal peptide. J Pharm Pharmacol. 2002 Nov;54(11):1559-63. doi: 10.1211/002235702117.
• [11] NO-induced migraine attack: strong increase in plasma calcitonin gene-related peptide (CGRP) concentration and negative correlation with platelet serotonin release. Pain. 2003 Dec;106(3):461-470. doi: 10.1016/j.pain.2003.09.008.
• [12] Upregulation of genes orchestrating keratinocyte differentiation, including the novel marker gene ID2, by contact sensitizers in human bulge-derived keratinocytes. J Biochem Mol Toxicol. 2010 Jan-Feb;24(1):10-20.
• [13] 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.
• [14] Enhancement of salivary secretion and neuropeptide (substance P, alpha-calcitonin gene-related peptide) levels in saliva by chronic anethole trithione treatment. J Pharm Pharmacol. 2001 Dec;53(12):1697-702. doi: 10.1211/0022357011778098.
• [15] 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.
• [16] Tryptanthrin induces growth inhibition and neuronal differentiation in the human neuroblastoma LA-N-1 cells. Chem Biol Interact. 2013 Apr 25;203(2):512-21. doi: 10.1016/j.cbi.2013.03.001. Epub 2013 Mar 13.
• [17] Calcitonin induces apoptosis resistance in prostate cancer cell lines against cytotoxic drugs via the Akt/survivin pathway. Cancer Biol Ther. 2005 Nov;4(11):1226-33. doi: 10.4161/cbt.4.11.2093. Epub 2005 Nov 5.
• [18] Volatile anesthetics inhibit calcitonin gene-related peptide receptor-mediated responses in pithed rats and human neuroblastoma cells. J Pharmacol Exp Ther. 2004 Dec;311(3):1016-22. doi: 10.1124/jpet.104.071936. Epub 2004 Aug 5.