Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX580VU)

• DOT Name: CD302 antigen (CD302)
• Synonyms: C-type lectin BIMLEC; C-type lectin domain family 13 member A; DEC205-associated C-type lectin 1; Type I transmembrane C-type lectin receptor DCL-1; CD antigen CD302
• Gene Name: CD302
• Related Disease:
  Acute myelogenous leukaemia
  Carcinoma
  Classic Hodgkin lymphoma
  Metastatic malignant neoplasm
  Neuroendocrine neoplasm
  Prostate carcinoma
• UniProt ID: CD302_HUMAN
• PDB ID: 2NAN
• Pfam ID: PF00059
• Sequence:
  MLRAALPALLLPLLGLAAAAVADCPSSTWIQFQDSCYIFLQEAIKVESIEDVRNQCTDHG
  ADMISIHNEEENAFILDTLKKQWKGPDDILLGMFYDTDDASFKWFDNSNMTFDKWTDQDD
  DEDLVDTCAFLHIKTGEWKKGNCEVSSVEGTLCKTAIPYKRKYLSDNHILISALVIASTV
  ILTVLGAIIWFLYKKHSDSRFTTVFSTAPQSPYNEDCVLVVGEENEYPVQFD
• Function: Potential multifunctional C-type lectin receptor that may play roles in endocytosis and phagocytosis as well as in cell adhesion and migration.
• Tissue Specificity: Expressed at moderate levels in monocytes, myeloid blood dendritic cells and granulocytes and at low levels in plasmacytoid blood dendritic cells, monocyte-derived ma crophages and monocyte-derived dendritic cells, with no expression detected in T-lymphocytes, B-lymphocytes and natural killer cells (at protein level). Expressed widely in different tissues, with highest expression levels in liver, lung, peripheral blood leukocytes and spleen, and lowest levels in neuronal tissues, skeletal muscle and ovary. Isoform 2 and isoform 3 are expressed in malignant Hodgkin lymphoma cells called Hodgkin and Reed-Sternberg (HRS) cells.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
Carcinoma	DISH9F1N	Strong	Altered Expression	[2]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Altered Expression	[3]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[4]
Neuroendocrine neoplasm	DISNPLOO	Strong	Altered Expression	[4]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	CD302 antigen (CD302) affects the response to substance of Methotrexate.	[22]

17 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 CD302 antigen (CD302).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of CD302 antigen (CD302).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of CD302 antigen (CD302).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CD302 antigen (CD302).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of CD302 antigen (CD302).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of CD302 antigen (CD302).	[10]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of CD302 antigen (CD302).	[11]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of CD302 antigen (CD302).	[12]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of CD302 antigen (CD302).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of CD302 antigen (CD302).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of CD302 antigen (CD302).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of CD302 antigen (CD302).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of CD302 antigen (CD302).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of CD302 antigen (CD302).	[18]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of CD302 antigen (CD302).	[19]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of CD302 antigen (CD302).	[20]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of CD302 antigen (CD302).	[21]

References

• [1] Examination of CD302 as a potential therapeutic target for acute myeloid leukemia.PLoS One. 2019 May 10;14(5):e0216368. doi: 10.1371/journal.pone.0216368. eCollection 2019.
• [2] Aberrant methylation and deacetylation of deleted in liver cancer-1 gene in prostate cancer: potential clinical applications.Clin Cancer Res. 2006 Mar 1;12(5):1412-9. doi: 10.1158/1078-0432.CCR-05-1906.
• [3] Hodgkin's lymphoma cell lines express a fusion protein encoded by intergenically spliced mRNA for the multilectin receptor DEC-205 (CD205) and a novel C-type lectin receptor DCL-1.J Biol Chem. 2003 Sep 5;278(36):34035-41. doi: 10.1074/jbc.M303112200. Epub 2003 Jun 24.
• [4] The search for the primary tumor in metastasized gastroenteropancreatic neuroendocrine neoplasm.Clin Exp Metastasis. 2014 Oct;31(7):817-27. doi: 10.1007/s10585-014-9672-3. Epub 2014 Aug 7.
• [5] 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.
• [6] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [11] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [12] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [13] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [14] 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.
• [15] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [16] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [17] 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.
• [18] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [19] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.
• [20] MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.
• [21] Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):73-88.
• [22] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.