Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJVN41C)

• DOT Name: Protein ADM2 (ADM2)
• Synonyms: Intermedin
• Gene Name: ADM2
• UniProt ID: ADM2_HUMAN
• PDB ID: 6D1U; 6UVA
• Sequence:
  MARIPTAALGCISLLCLQLPGSLSRSLGGDPRPVKPREPPARSPSSSLQPRHPAPRPVVW
  KLHRALQAQRGAGLAPVMGQPLRDGGRQHSGPRRHSGPRRTQAQLLRVGCVLGTCQVQNL
  SHRLWQLMGPAGRQDSAPVDPSSPHSYG
• Function: [Adrenomedullin-2]: May play a role as physiological regulators of gastrointestinal, cardiovascular bioactivities mediated by the CALCRL/RAMPs receptor complexes. Activates the cAMP-dependent pathway; [Intermedin-short]: May play a role as physiological regulators of gastrointestinal, cardiovascular bioactivities mediated by the CALCRL/RAMPs receptor complexes. Activates the cAMP-dependent pathway.
• Tissue Specificity: Expressed in the esophagus, stomach, jejunum, ileum, ileocecum, ascending colon, transverse colon, descending colon and rectum. Expressed in myocardial cells of the heart, renal tubular cells, hypothalamus, and pituitary.
• 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

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 Protein ADM2 (ADM2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein ADM2 (ADM2).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Protein ADM2 (ADM2).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein ADM2 (ADM2).	[3]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Protein ADM2 (ADM2).	[2]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Protein ADM2 (ADM2).	[4]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Protein ADM2 (ADM2).	[5]
Urethane	DM7NSI0	Phase 4	Urethane affects the expression of Protein ADM2 (ADM2).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein ADM2 (ADM2).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Protein ADM2 (ADM2).	[9]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Protein ADM2 (ADM2).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein ADM2 (ADM2).	[11]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone decreases the expression of Protein ADM2 (ADM2).	[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] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [3] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [4] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [5] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [8] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [11] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
• [12] 3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.