Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2DROYU)

• DOT Name: Repulsive guidance molecule B (RGMB)
• Synonyms: DRG11-responsive axonal guidance and outgrowth of neurite; DRAGON
• Gene Name: RGMB
• Related Disease:
  Advanced cancer
  Hemochromatosis type 2
  Multiple sclerosis
  Breast cancer
  Breast carcinoma
  Cerebral infarction
  Colorectal carcinoma
  Non-small-cell lung cancer
  Obesity
  Prostate cancer
  Prostate neoplasm
  Stroke
  Lung adenocarcinoma
  Asthma
  Hepatocellular carcinoma
  Rheumatoid arthritis
• UniProt ID: RGMB_HUMAN
• PDB ID: 4BQ6; 4BQ7; 4BQ8; 4UHZ; 4UI0; 4UI2; 6Z3H; 6Z3J; 6Z3M
• Pfam ID: PF06534 ; PF06535
• Sequence:
  MGLRAAPSSAAAAAAEVEQRRSPGLCPPPLELLLLLLFSLGLLHAGDCQQPAQCRIQKCT
  TDFVSLTSHLNSAVDGFDSEFCKALRAYAGCTQRTSKACRGNLVYHSAVLGISDLMSQRN
  CSKDGPTSSTNPEVTHDPCNYHSHAGAREHRRGDQNPPSYLFCGLFGDPHLRTFKDNFQT
  CKVEGAWPLIDNNYLSVQVTNVPVVPGSSATATNKITIIFKAHHECTDQKVYQAVTDDLP
  AAFVDGTTSGGDSDAKSLRIVERESGHYVEMHARYIGTTVFVRQVGRYLTLAIRMPEDLA
  MSYEESQDLQLCVNGCPLSERIDDGQGQVSAILGHSLPRTSLVQAWPGYTLETANTQCHE
  KMPVKDIYFQSCVFDLLTTGDANFTAAAHSALEDVEALHPRKERWHIFPSSGNGTPRGGS
  DLSVSLGLTCLILIVFL
• Function: Member of the repulsive guidance molecule (RGM) family that contributes to the patterning of the developing nervous system. Acts as a bone morphogenetic protein (BMP) coreceptor that potentiates BMP signaling. Promotes neuronal adhesion. May inhibit neurite outgrowth.
• KEGG Pathway: TGF-beta sig.ling pathway (hsa04350)
• Reactome Pathway: Netrin-1 signaling (R-HSA-373752)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]
Hemochromatosis type 2	DISYM9UP	Definitive	Biomarker	[1]
Multiple sclerosis	DISB2WZI	Definitive	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Cerebral infarction	DISR1WNP	Strong	Altered Expression	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[5]
Obesity	DIS47Y1K	Strong	Biomarker	[6]
Prostate cancer	DISF190Y	Strong	Biomarker	[7]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[7]
Stroke	DISX6UHX	Strong	Biomarker	[8]
Lung adenocarcinoma	DISD51WR	moderate	Altered Expression	[9]
Asthma	DISW9QNS	Limited	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[11]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Repulsive guidance molecule B (RGMB).	[13]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Repulsive guidance molecule B (RGMB).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Repulsive guidance molecule B (RGMB).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Repulsive guidance molecule B (RGMB).	[16]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Repulsive guidance molecule B (RGMB).	[17]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Repulsive guidance molecule B (RGMB).	[19]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Repulsive guidance molecule B (RGMB).	[20]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Repulsive guidance molecule B (RGMB).	[21]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Repulsive guidance molecule B (RGMB).	[22]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Repulsive guidance molecule B (RGMB).	[21]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Repulsive guidance molecule B (RGMB).	[23]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Repulsive guidance molecule B (RGMB).	[24]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Repulsive guidance molecule B (RGMB).	[25]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Repulsive guidance molecule B (RGMB).	[26]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Repulsive guidance molecule B (RGMB).	[27]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Repulsive guidance molecule B (RGMB).	[22]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Repulsive guidance molecule B (RGMB).	[29]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Repulsive guidance molecule B (RGMB).	[30]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Repulsive guidance molecule B (RGMB).	[31]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Repulsive guidance molecule B (RGMB).	[32]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Repulsive guidance molecule B (RGMB).	[33]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Repulsive guidance molecule B (RGMB).	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Repulsive guidance molecule B (RGMB).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Repulsive guidance molecule B (RGMB).	[28]

References

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• [12] Distinctive gene expression signatures in rheumatoid arthritis synovial tissue fibroblast cells: correlates with disease activity.Genes Immun. 2007 Sep;8(6):480-91. doi: 10.1038/sj.gene.6364400. Epub 2007 Jun 14.
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• [22] 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.
• [23] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
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• [25] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
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• [27] 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.
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• [34] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.