Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRWG9QS)

• DOT Name: Cell adhesion molecule 1 (CADM1)
• Synonyms: Immunoglobulin superfamily member 4; IgSF4; Nectin-like protein 2; NECL-2; Spermatogenic immunoglobulin superfamily; SgIgSF; Synaptic cell adhesion molecule; SynCAM; Tumor suppressor in lung cancer 1; TSLC-1
• Gene Name: CADM1
• Related Disease:
  Adult T-cell leukemia/lymphoma
  Colorectal carcinoma
  Lung neoplasm
  Melanoma
  Meningioma
  Acute myelogenous leukaemia
  Adenocarcinoma
  Advanced cancer
  Anorexia nervosa cachexia
  Autism
  B-cell neoplasm
  Bladder cancer
  Breast neoplasm
  Carcinoma
  Carcinoma of liver and intrahepatic biliary tract
  Cervical Intraepithelial neoplasia
  Colon cancer
  Depression
  Esophageal squamous cell carcinoma
  Gastric cancer
  Glioblastoma multiforme
  Glioma
  Laryngeal squamous cell carcinoma
  Liver cancer
  Meningitis
  Mycosis fungoides
  Nasopharyngeal carcinoma
  Neuroblastoma
  Non-small-cell lung cancer
  Prostate carcinoma
  Pulmonary emphysema
  Small-cell lung cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Cutaneous melanoma
  Nephropathy
  Squamous cell carcinoma
  T-cell leukaemia
  Autism spectrum disorder
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
  Obesity
  Prostate cancer
  Stomach cancer
• UniProt ID: CADM1_HUMAN
• PDB ID: 3BIN; 4H5S
• Pfam ID: PF08205 ; PF13927 ; PF07686
• Sequence:
  MASVVLPSGSQCAAAAAAAAPPGLRLRLLLLLFSAAALIPTGDGQNLFTKDVTVIEGEVA
  TISCQVNKSDDSVIQLLNPNRQTIYFRDFRPLKDSRFQLLNFSSSELKVSLTNVSISDEG
  RYFCQLYTDPPQESYTTITVLVPPRNLMIDIQKDTAVEGEEIEVNCTAMASKPATTIRWF
  KGNTELKGKSEVEEWSDMYTVTSQLMLKVHKEDDGVPVICQVEHPAVTGNLQTQRYLEVQ
  YKPQVHIQMTYPLQGLTREGDALELTCEAIGKPQPVMVTWVRVDDEMPQHAVLSGPNLFI
  NNLNKTDNGTYRCEASNIVGKAHSDYMLYVYDPPTTIPPPTTTTTTTTTTTTTILTIITD
  SRAGEEGSIRAVDHAVIGGVVAVVVFAMLCLLIILGRYFARHKGTYFTHEAKGADDAADA
  DTAIINAEGGQNNSEEKKEYFI
• Function: Mediates homophilic cell-cell adhesion in a Ca(2+)-independent manner. Also mediates heterophilic cell-cell adhesion with CADM3 and NECTIN3 in a Ca(2+)-independent manner. Interaction with CRTAM promotes natural killer (NK) cell cytotoxicity and interferon-gamma (IFN-gamma) secretion by CD8+ cells in vitro as well as NK cell-mediated rejection of tumors expressing CADM1 in vivo. In mast cells, may mediate attachment to and promote communication with nerves. CADM1, together with MITF, is essential for development and survival of mast cells in vivo. By interacting with CRTAM and thus promoting the adhesion between CD8+ T-cells and CD8+ dendritic cells, regulates the retention of activated CD8+ T-cell within the draining lymph node. Required for the intestinal retention of intraepithelial CD4+ CD8+ T-cells and, to a lesser extent, intraepithelial and lamina propria CD8+ T-cells and CD4+ T-cells. Interaction with CRTAM promotes the adhesion to gut-associated CD103+ dendritic cells, which may facilitate the expression of gut-homing and adhesion molecules on T-cells and the conversion of CD4+ T-cells into CD4+ CD8+ T-cells. Acts as a synaptic cell adhesion molecule and plays a role in the formation of dendritic spines and in synapse assembly. May be involved in neuronal migration, axon growth, pathfinding, and fasciculation on the axons of differentiating neurons. May play diverse roles in the spermatogenesis including in the adhesion of spermatocytes and spermatids to Sertoli cells and for their normal differentiation into mature spermatozoa. Acts as a tumor suppressor in non-small-cell lung cancer (NSCLC) cells. May contribute to the less invasive phenotypes of lepidic growth tumor cells.
• KEGG Pathway: Cell adhesion molecules (hsa04514)
• Reactome Pathway:
  Nectin/Necl trans heterodimerization (R-HSA-420597)
  Adherens junctions interactions (R-HSA-418990)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult T-cell leukemia/lymphoma	DIS882XU	Definitive	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Definitive	Biomarker	[2]
Lung neoplasm	DISVARNB	Definitive	Altered Expression	[3]
Melanoma	DIS1RRCY	Definitive	Altered Expression	[4]
Meningioma	DISPT4TG	Definitive	Biomarker	[5]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[6]
Adenocarcinoma	DIS3IHTY	Strong	Posttranslational Modification	[7]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[8]
Anorexia nervosa cachexia	DISFO5RQ	Strong	Genetic Variation	[9]
Autism	DISV4V1Z	Strong	Genetic Variation	[10]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[11]
Bladder cancer	DISUHNM0	Strong	Biomarker	[11]
Breast neoplasm	DISNGJLM	Strong	Posttranslational Modification	[12]
Carcinoma	DISH9F1N	Strong	Posttranslational Modification	[13]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Posttranslational Modification	[14]
Cervical Intraepithelial neoplasia	DISXP757	Strong	Posttranslational Modification	[15]
Colon cancer	DISVC52G	Strong	Altered Expression	[16]
Depression	DIS3XJ69	Strong	Biomarker	[17]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[18]
Gastric cancer	DISXGOUK	Strong	Biomarker	[19]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[20]
Glioma	DIS5RPEH	Strong	Biomarker	[21]
Laryngeal squamous cell carcinoma	DIS9UUVF	Strong	Biomarker	[22]
Liver cancer	DISDE4BI	Strong	Posttranslational Modification	[14]
Meningitis	DISQABAA	Strong	Biomarker	[23]
Mycosis fungoides	DIS62RB8	Strong	Altered Expression	[24]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[25]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[26]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[27]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[28]
Pulmonary emphysema	DIS5M7HZ	Strong	Biomarker	[29]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[30]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[11]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[11]
Cutaneous melanoma	DIS3MMH9	moderate	Posttranslational Modification	[31]
Nephropathy	DISXWP4P	Disputed	Biomarker	[32]
Squamous cell carcinoma	DISQVIFL	Disputed	Biomarker	[33]
T-cell leukaemia	DISJ6YIF	Disputed	Altered Expression	[34]
Autism spectrum disorder	DISXK8NV	Limited	Autosomal dominant	[35]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[36]
Lung cancer	DISCM4YA	Limited	Altered Expression	[37]
Lung carcinoma	DISTR26C	Limited	Altered Expression	[37]
Obesity	DIS47Y1K	Limited	Biomarker	[38]
Prostate cancer	DISF190Y	Limited	Altered Expression	[39]
Stomach cancer	DISKIJSX	Limited	Biomarker	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Cell adhesion molecule 1 (CADM1) increases the response to substance of Arsenic.	[64]
DTI-015	DMXZRW0	Approved	Cell adhesion molecule 1 (CADM1) affects the response to substance of DTI-015.	[65]

23 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 Cell adhesion molecule 1 (CADM1).	[40]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cell adhesion molecule 1 (CADM1).	[41]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cell adhesion molecule 1 (CADM1).	[42]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cell adhesion molecule 1 (CADM1).	[43]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Cell adhesion molecule 1 (CADM1).	[44]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Cell adhesion molecule 1 (CADM1).	[45]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cell adhesion molecule 1 (CADM1).	[46]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Cell adhesion molecule 1 (CADM1).	[47]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Cell adhesion molecule 1 (CADM1).	[48]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Cell adhesion molecule 1 (CADM1).	[49]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Cell adhesion molecule 1 (CADM1).	[50]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cell adhesion molecule 1 (CADM1).	[51]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Cell adhesion molecule 1 (CADM1).	[52]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Cell adhesion molecule 1 (CADM1).	[12]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Cell adhesion molecule 1 (CADM1).	[25]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Cell adhesion molecule 1 (CADM1).	[55]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Cell adhesion molecule 1 (CADM1).	[56]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Cell adhesion molecule 1 (CADM1).	[42]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Cell adhesion molecule 1 (CADM1).	[58]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Cell adhesion molecule 1 (CADM1).	[59]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cell adhesion molecule 1 (CADM1).	[61]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Cell adhesion molecule 1 (CADM1).	[62]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Cell adhesion molecule 1 (CADM1).	[63]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cell adhesion molecule 1 (CADM1).	[57]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Cell adhesion molecule 1 (CADM1).	[60]

References

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