Details of Drug Off-Target (DOT)

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

• DOT Name: Early activation antigen CD69 (CD69)
• Synonyms: Activation inducer molecule; AIM; BL-AC/P26; C-type lectin domain family 2 member C; EA1; Early T-cell activation antigen p60; GP32/28; Leukocyte surface antigen Leu-23; MLR-3; CD antigen CD69
• Gene Name: CD69
• UniProt ID: CD69_HUMAN
• PDB ID: 1E87; 1E8I; 1FM5; 3CCK; 3HUP; 8G94
• Pfam ID: PF00059
• Sequence:
  MSSENCFVAENSSLHPESGQENDATSPHFSTRHEGSFQVPVLCAVMNVVFITILIIALIA
  LSVGQYNCPGQYTFSMPSDSHVSSCSEDWVGYQRKCYFISTVKRSWTSAQNACSEHGATL
  AVIDSEKDMNFLKRYAGREEHWVGLKKEPGHPWKWSNGKEFNNWFNVTGSDKCVFLKNTE
  VSSMECEKNLYWICNKPYK
• Function: Involved in lymphocyte proliferation and functions as a signal transmitting receptor in lymphocytes, natural killer (NK) cells, and platelets.
• Tissue Specificity: Expressed on the surface of activated T-cells, B-cells, natural killer cells, neutrophils, eosinophils, epidermal Langerhans cells and platelets.

Molecular Interaction Atlas (MIA) of This DOT

24 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 Early activation antigen CD69 (CD69).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Early activation antigen CD69 (CD69).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Early activation antigen CD69 (CD69).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Early activation antigen CD69 (CD69).	[4]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Early activation antigen CD69 (CD69).	[5]
Marinol	DM70IK5	Approved	Marinol increases the expression of Early activation antigen CD69 (CD69).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Early activation antigen CD69 (CD69).	[7]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Early activation antigen CD69 (CD69).	[8]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Early activation antigen CD69 (CD69).	[9]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Early activation antigen CD69 (CD69).	[10]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Early activation antigen CD69 (CD69).	[11]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Early activation antigen CD69 (CD69).	[12]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Early activation antigen CD69 (CD69).	[2]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Early activation antigen CD69 (CD69).	[13]
Lindane	DMB8CNL	Approved	Lindane increases the expression of Early activation antigen CD69 (CD69).	[2]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Early activation antigen CD69 (CD69).	[14]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Early activation antigen CD69 (CD69).	[3]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Early activation antigen CD69 (CD69).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Early activation antigen CD69 (CD69).	[2]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Early activation antigen CD69 (CD69).	[16]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Early activation antigen CD69 (CD69).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Early activation antigen CD69 (CD69).	[9]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Early activation antigen CD69 (CD69).	[2]
PROSTRATIN	DM1HMJ5	Investigative	PROSTRATIN increases the expression of Early activation antigen CD69 (CD69).	[18]

References

• [1] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [2] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [3] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [4] Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women. Arch Toxicol. 2017 May;91(5):2067-2078. doi: 10.1007/s00204-016-1879-4. Epub 2016 Nov 12.
• [5] Epigenetic silencing of novel tumor suppressors in malignant melanoma. Cancer Res. 2006 Dec 1;66(23):11187-93. doi: 10.1158/0008-5472.CAN-06-1274.
• [6] Cannabis-induced cytotoxicity in leukemic cell lines: the role of the cannabinoid receptors and the MAPK pathway. Blood. 2005 Feb 1;105(3):1214-21. doi: 10.1182/blood-2004-03-1182. Epub 2004 Sep 28.
• [7] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [8] Gene expression profile of human lymphoid CEM cells sensitive and resistant to glucocorticoid-evoked apoptosis. Genomics. 2003 Jun;81(6):543-55.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [10] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [11] Dasatinib, a small-molecule protein tyrosine kinase inhibitor, inhibits T-cell activation and proliferation. Blood. 2008 Feb 1;111(3):1366-77. doi: 10.1182/blood-2007-04-084814. Epub 2007 Oct 25.
• [12] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [13] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [14] Resveratrol induces apoptosis in transformed follicular lymphoma OCI-LY8 cells: evidence for a novel mechanism involving inhibition of BCL6 signaling. Int J Oncol. 2006 Dec;29(6):1561-6.
• [15] Expression of endogenous retroviruses reflects increased usage of atypical enhancers in T cells. EMBO J. 2019 Jun 17;38(12):e101107. doi: 10.15252/embj.2018101107. Epub 2019 May 8.
• [16] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [17] DON shares a similar mode of action as the ribotoxic stress inducer anisomycin while TBTO shares ER stress patterns with the ER stress inducer thapsigargin based on comparative gene expression profiling in Jurkat T cells. Toxicol Lett. 2014 Jan 30;224(3):395-406. doi: 10.1016/j.toxlet.2013.11.005. Epub 2013 Nov 15.
• [18] The BET inhibitor OTX015 reactivates latent HIV-1 through P-TEFb. Sci Rep. 2016 Apr 12;6:24100. doi: 10.1038/srep24100.