Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUFSBX2)

DOT Name	C-X-C chemokine receptor type 4 (CXCR4)
Synonyms	CXC-R4; CXCR-4; FB22; Fusin; HM89; LCR1; Leukocyte-derived seven transmembrane domain receptor; LESTR; Lipopolysaccharide-associated protein 3; LAP-3; LPS-associated protein 3; NPYRL; Stromal cell-derived factor 1 receptor; SDF-1 receptor; CD antigen CD184
Gene Name	CXCR4
Related Disease	Whim syndrome ( ) WHIM syndrome 1 ( ) Obsolete WHIM syndrome ( )
UniProt ID	CXCR4_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2K03; 2K04; 2K05; 2N55; 3ODU; 3OE0; 3OE6; 3OE8; 3OE9; 4RWS; 8GP3; 8I0Q
Pfam ID	PF00001 ; PF12109
Sequence	MEGISIYTSDNYTEEMGSGDYDSMKEPCFREENANFNKIFLPTIYSIIFLTGIVGNGLVI LVMGYQKKLRSMTDKYRLHLSVADLLFVITLPFWAVDAVANWYFGNFLCKAVHVIYTVNL YSSVLILAFISLDRYLAIVHATNSQRPRKLLAEKVVYVGVWIPALLLTIPDFIFANVSEA DDRYICDRFYPNDLWVVVFQFQHIMVGLILPGIVILSCYCIIISKLSHSKGHQKRKALKT TVILILAFFACWLPYYIGISIDSFILLEIIKQGCEFENTVHKWISITEALAFFHCCLNPI LYAFLGAKFKTSAQHALTSVSRGSSLKILSKGKRGGHSSVSTESESSSFHSS
Function	Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Involved in the AKT signaling cascade. Plays a role in regulation of cell migration, e.g. during wound healing. Acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels. Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion by monocytes. Involved in hematopoiesis and in cardiac ventricular septum formation. Also plays an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells. Involved in cerebellar development. In the CNS, could mediate hippocampal-neuron survival; (Microbial infection) Acts as a coreceptor (CD4 being the primary receptor) for human immunodeficiency virus-1/HIV-1 X4 isolates and as a primary receptor for some HIV-2 isolates. Promotes Env-mediated fusion of the virus.
Tissue Specificity	Expressed in numerous tissues, such as peripheral blood leukocytes, spleen, thymus, spinal cord, heart, placenta, lung, liver, skeletal muscle, kidney, pancreas, cerebellum, cerebral cortex and medulla (in microglia as well as in astrocytes), brain microvascular, coronary artery and umbilical cord endothelial cells. Isoform 1 is predominant in all tissues tested.
KEGG Pathway	Viral life cycle - HIV-1 (hsa03250 ) Virion - Human immunodeficiency virus (hsa03260 ) Calcium sig.ling pathway (hsa04020 ) Cytokine-cytokine receptor interaction (hsa04060 ) Viral protein interaction with cytokine and cytokine receptor (hsa04061 ) Chemokine sig.ling pathway (hsa04062 ) Endocytosis (hsa04144 ) Axon guidance (hsa04360 ) Leukocyte transendothelial migration (hsa04670 ) Intesti.l immune network for IgA production (hsa04672 ) Regulation of actin cytoskeleton (hsa04810 ) Human cytomegalovirus infection (hsa05163 ) Human immunodeficiency virus 1 infection (hsa05170 ) Pathways in cancer (hsa05200 )
Reactome Pathway	Signaling by ROBO receptors (R-HSA-376176 ) Chemokine receptors bind chemokines (R-HSA-380108 ) G alpha (i) signalling events (R-HSA-418594 ) Formation of definitive endoderm (R-HSA-9823730 ) Specification of primordial germ cells (R-HSA-9827857 ) Binding and entry of HIV virion (R-HSA-173107 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Whim syndrome	DIS8J18X	Definitive	Autosomal dominant	[1]
WHIM syndrome 1	DISFNJOB	Definitive	Autosomal dominant	[2]
Obsolete WHIM syndrome	DISIM7F9	Moderate	Autosomal dominant	[3]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	C-X-C chemokine receptor type 4 (CXCR4) decreases the response to substance of Paclitaxel.	[60]
Genistein	DM0JETC	Phase 2/3	C-X-C chemokine receptor type 4 (CXCR4) decreases the response to substance of Genistein.	[61]
HPTE	DMRPZD4	Investigative	C-X-C chemokine receptor type 4 (CXCR4) decreases the response to substance of HPTE.	[61]
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66 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 C-X-C chemokine receptor type 4 (CXCR4).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of C-X-C chemokine receptor type 4 (CXCR4).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of C-X-C chemokine receptor type 4 (CXCR4).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[14]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[13]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[15]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[16]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of C-X-C chemokine receptor type 4 (CXCR4).	[17]
Marinol	DM70IK5	Approved	Marinol increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[18]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[19]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of C-X-C chemokine receptor type 4 (CXCR4).	[20]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[21]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[22]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[23]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[16]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[24]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[16]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[25]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[16]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[26]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[27]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[28]
Gemcitabine	DMSE3I7	Approved	Gemcitabine affects the expression of C-X-C chemokine receptor type 4 (CXCR4).	[29]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[16]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[30]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[31]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[16]
Dinoprostone	DMTYOPD	Approved	Dinoprostone increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[32]
Ardeparin	DMYRX8B	Approved	Ardeparin decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[33]
Propofol	DMB4OLE	Approved	Propofol decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[34]
Sevoflurane	DMC9O43	Approved	Sevoflurane increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[34]
Omeprazole	DM471KJ	Approved	Omeprazole decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[35]
Etodolac	DM6WJO9	Approved	Etodolac decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[36]
Carfilzomib	DM48K0X	Approved	Carfilzomib decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[37]
Tranilast	DME5Y64	Approved	Tranilast decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[35]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[38]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[39]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[40]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[41]
Coprexa	DMA0WEK	Phase 3	Coprexa increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[42]
DNCB	DMDTVYC	Phase 2	DNCB decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[43]
PBI-05204	DM05WIU	Phase 2	PBI-05204 increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[44]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[46]
GSK618334	DMJPXZ4	Phase 1	GSK618334 decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[47]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[48]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[49]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[50]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[52]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[53]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[54]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[55]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[56]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[57]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[43]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[58]
Cordycepin	DM72Y01	Investigative	Cordycepin decreases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[59]
Methyl Mercury Ion	DM6YEW4	Investigative	Methyl Mercury Ion increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[54]
benzyl bromide	DM857X2	Investigative	benzyl bromide increases the expression of C-X-C chemokine receptor type 4 (CXCR4).	[26]
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⏷ Show the Full List of 66 Drug(s)

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 C-X-C chemokine receptor type 4 (CXCR4).	[45]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of C-X-C chemokine receptor type 4 (CXCR4).	[51]
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