Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5OFDJC)

• DOT Name: Annexin A1 (ANXA1)
• Synonyms: Annexin I; Annexin-1; Calpactin II; Calpactin-2; Chromobindin-9; Lipocortin I; Phospholipase A2 inhibitory protein; p35
• Gene Name: ANXA1
• UniProt ID: ANXA1_HUMAN
• PDB ID: 1AIN; 1BO9; 1QLS; 5VFW
• Pfam ID: PF00191
• Sequence:
  MAMVSEFLKQAWFIENEEQEYVQTVKSSKGGPGSAVSPYPTFNPSSDVAALHKAIMVKGV
  DEATIIDILTKRNNAQRQQIKAAYLQETGKPLDETLKKALTGHLEEVVLALLKTPAQFDA
  DELRAAMKGLGTDEDTLIEILASRTNKEIRDINRVYREELKRDLAKDITSDTSGDFRNAL
  LSLAKGDRSEDFGVNEDLADSDARALYEAGERRKGTDVNVFNTILTTRSYPQLRRVFQKY
  TKYSKHDMNKVLDLELKGDIEKCLTAIVKCATSKPAFFAEKLHQAMKGVGTRHKALIRIM
  VSRSEIDMNDIKAFYQKMYGISLCQAILDETKGDYEKILVALCGGN
• Function: Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity. Plays a role in glucocorticoid-mediated down-regulation of the early phase of the inflammatory response. Contributes to the adaptive immune response by enhancing signaling cascades that are triggered by T-cell activation, regulates differentiation and proliferation of activated T-cells. Promotes the differentiation of T-cells into Th1 cells and negatively regulates differentiation into Th2 cells. Has no effect on unstimulated T cells. Negatively regulates hormone exocytosis via activation of the formyl peptide receptors and reorganization of the actin cytoskeleton. Has high affinity for Ca(2+) and can bind up to eight Ca(2+) ions. Displays Ca(2+)-dependent binding to phospholipid membranes. Plays a role in the formation of phagocytic cups and phagosomes. Plays a role in phagocytosis by mediating the Ca(2+)-dependent interaction between phagosomes and the actin cytoskeleton; [Annexin Ac2-26]: Functions at least in part by activating the formyl peptide receptors and downstream signaling cascades. Promotes chemotaxis of granulocytes and monocytes via activation of the formyl peptide receptors. Promotes rearrangement of the actin cytoskeleton, cell polarization and cell migration. Promotes resolution of inflammation and wound healing. Acts via neutrophil N-formyl peptide receptors to enhance the release of CXCL2.
• Tissue Specificity: Detected in resting neutrophils . Detected in peripheral blood T-cells . Detected in extracellular vesicles in blood serum from patients with inflammatory bowel disease, but not in serum from healthy donors . Detected in placenta (at protein level) . Detected in liver.
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Formyl peptide receptors bind formyl peptides and many other ligands (R-HSA-444473)
  Smooth Muscle Contraction (R-HSA-445355)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  G alpha (q) signalling events (R-HSA-416476)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Annexin A1 (ANXA1) increases the response to substance of Paclitaxel.	[51]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Annexin A1 (ANXA1).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Annexin A1 (ANXA1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Annexin A1 (ANXA1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Annexin A1 (ANXA1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Annexin A1 (ANXA1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Annexin A1 (ANXA1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Annexin A1 (ANXA1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Annexin A1 (ANXA1).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Annexin A1 (ANXA1).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Annexin A1 (ANXA1).	[10]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Annexin A1 (ANXA1).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Annexin A1 (ANXA1).	[12]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Annexin A1 (ANXA1).	[13]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Annexin A1 (ANXA1).	[14]
Marinol	DM70IK5	Approved	Marinol increases the expression of Annexin A1 (ANXA1).	[15]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Annexin A1 (ANXA1).	[16]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Annexin A1 (ANXA1).	[17]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Annexin A1 (ANXA1).	[18]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Annexin A1 (ANXA1).	[19]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Annexin A1 (ANXA1).	[20]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Annexin A1 (ANXA1).	[21]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone affects the expression of Annexin A1 (ANXA1).	[22]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Annexin A1 (ANXA1).	[23]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Annexin A1 (ANXA1).	[24]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Annexin A1 (ANXA1).	[25]
Ibuprofen	DM8VCBE	Approved	Ibuprofen affects the expression of Annexin A1 (ANXA1).	[26]
Acocantherin	DM7JT24	Approved	Acocantherin affects the expression of Annexin A1 (ANXA1).	[27]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone increases the expression of Annexin A1 (ANXA1).	[28]
Rofecoxib	DM3P5DA	Approved	Rofecoxib affects the expression of Annexin A1 (ANXA1).	[26]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Annexin A1 (ANXA1).	[18]
Bardoxolone methyl	DMODA2X	Phase 3	Bardoxolone methyl affects the expression of Annexin A1 (ANXA1).	[30]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Annexin A1 (ANXA1).	[31]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Annexin A1 (ANXA1).	[32]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin increases the expression of Annexin A1 (ANXA1).	[33]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Annexin A1 (ANXA1).	[34]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Annexin A1 (ANXA1).	[35]
AMEP	DMFELMQ	Phase 1	AMEP increases the expression of Annexin A1 (ANXA1).	[36]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Annexin A1 (ANXA1).	[37]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Annexin A1 (ANXA1).	[38]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Annexin A1 (ANXA1).	[39]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Annexin A1 (ANXA1).	[40]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Annexin A1 (ANXA1).	[20]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Annexin A1 (ANXA1).	[41]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Annexin A1 (ANXA1).	[42]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Annexin A1 (ANXA1).	[43]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Annexin A1 (ANXA1).	[44]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Annexin A1 (ANXA1).	[36]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Annexin A1 (ANXA1).	[45]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Annexin A1 (ANXA1).	[46]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid increases the expression of Annexin A1 (ANXA1).	[47]
Aminohippuric acid	DMUN54G	Investigative	Aminohippuric acid affects the expression of Annexin A1 (ANXA1).	[48]
ORG2058	DMH1M6N	Investigative	ORG2058 increases the expression of Annexin A1 (ANXA1).	[49]
4-[1-(4-hydroxyphenyl)-2-phenylbut-1-enyl]phenol	DMTMLXU	Investigative	4-[1-(4-hydroxyphenyl)-2-phenylbut-1-enyl]phenol increases the expression of Annexin A1 (ANXA1).	[50]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluticasone propionate	DMRWLB2	Approved	Fluticasone propionate affects the localization of Annexin A1 (ANXA1).	[29]

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