Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNVY7WY)

• DOT Name: Calcitonin gene-related peptide 2 (CALCB)
• Synonyms: Beta-type CGRP; Beta-CGRP; Calcitonin gene-related peptide II; CGRP-II
• Gene Name: CALCB
• UniProt ID: CALCB_HUMAN
• Pfam ID: PF00214
• Sequence:
  MGFRKFSPFLALSILVLYQAGSLQAAPFRSALESSPDPATLSKEDARLLLAALVQDYVQM
  KASELKQEQETQGSSSAAQKRACNTATCVTHRLAGLLSRSGGMVKSNFVPTNVGSKAFGR
  RRRDLQA
• Function: CGRP induces vasodilation. It dilates a variety of vessels including the coronary, cerebral and systemic vasculature. Its abundance in the CNS also points toward a neurotransmitter or neuromodulator role.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Vascular smooth muscle contraction (hsa04270)
• Reactome Pathway:
  Calcitonin-like ligand receptors (R-HSA-419812)
  G alpha (s) signalling events (R-HSA-418555)

Molecular Interaction Atlas (MIA) of This DOT

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 Calcitonin gene-related peptide 2 (CALCB).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Calcitonin gene-related peptide 2 (CALCB).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Calcitonin gene-related peptide 2 (CALCB).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Calcitonin gene-related peptide 2 (CALCB).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Calcitonin gene-related peptide 2 (CALCB).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Calcitonin gene-related peptide 2 (CALCB).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Calcitonin gene-related peptide 2 (CALCB).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Calcitonin gene-related peptide 2 (CALCB).	[6]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Calcitonin gene-related peptide 2 (CALCB).	[7]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Calcitonin gene-related peptide 2 (CALCB).	[8]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Calcitonin gene-related peptide 2 (CALCB).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Calcitonin gene-related peptide 2 (CALCB).	[12]

References

• [1] 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.
• [2] Molecular characterization of a toxicological tipping point during human stem cell differentiation. Reprod Toxicol. 2020 Jan;91:1-13. doi: 10.1016/j.reprotox.2019.10.001. Epub 2019 Oct 7.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [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] 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.
• [10] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [11] 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.
• [12] 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.