Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2QX5LL)

• DOT Name: Stromal cell-derived factor 1 (CXCL12)
• Synonyms: SDF-1; hSDF-1; C-X-C motif chemokine 12; Intercrine reduced in hepatomas; IRH; hIRH; Pre-B cell growth-stimulating factor; PBSF
• Gene Name: CXCL12
• UniProt ID: SDF1_HUMAN
• PDB ID: 1A15; 1QG7; 1SDF; 1VMC; 2J7Z; 2K01; 2K03; 2K04; 2K05; 2KEC; 2KED; 2KEE; 2KOL; 2N55; 2NWG; 2SDF; 3GV3; 3HP3; 4LMQ; 4UAI; 6SHR; 7SK3; 7SK4; 7SK5; 7SK6; 7SK7; 7SK8
• Pfam ID: PF00048
• Sequence:
  MNAKVVVVLVLVLTALCLSDGKPVSLSYRCPCRFFESHVARANVKHLKILNTPNCALQIV
  ARLKNNNRQVCIDPKLKWIQEYLEKALNKRFKM
• Function: Chemoattractant active on T-lymphocytes and monocytes but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. SDF-1-beta(3-72) and SDF-1-alpha(3-67) show a reduced chemotactic activity. Binding to cell surface proteoglycans seems to inhibit formation of SDF-1-alpha(3-67) and thus to preserve activity on local sites. Also binds to atypical chemokine receptor ACKR3, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. Binds to the allosteric site (site 2) of integrins and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1 in a CXCR4-independent manner. Acts as a positive regulator of monocyte migration and a negative regulator of monocyte adhesion via the LYN kinase. Stimulates migration of monocytes and T-lymphocytes through its receptors, CXCR4 and ACKR3, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for beta-2 integrins. SDF1A/CXCR4 signaling axis inhibits beta-2 integrin LFA-1 mediated adhesion of monocytes to ICAM-1 through LYN kinase. Inhibits CXCR4-mediated infection by T-cell line-adapted HIV-1. Plays a protective role after myocardial infarction. Induces down-regulation and internalization of ACKR3 expressed in various cells. Has several critical functions during embryonic development; required for B-cell lymphopoiesis, myelopoiesis in bone marrow and heart ventricular septum formation. Stimulates the proliferation of bone marrow-derived B-cell progenitors in the presence of IL7 as well as growth of stromal cell-dependent pre-B-cells.
• Tissue Specificity: Isoform Alpha and isoform Beta are ubiquitously expressed, with highest levels detected in liver, pancreas and spleen. Isoform Gamma is mainly expressed in heart, with weak expression detected in several other tissues. Isoform Delta, isoform Epsilon and isoform Theta have highest expression levels in pancreas, with lower levels detected in heart, kidney, liver and spleen.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  Chemokine sig.ling pathway (hsa04062)
  NF-kappa B sig.ling pathway (hsa04064)
  Axon guidance (hsa04360)
  Leukocyte transendothelial migration (hsa04670)
  Intesti.l immune network for IgA production (hsa04672)
  Regulation of actin cytoskeleton (hsa04810)
  Human cytomegalovirus infection (hsa05163)
  Pathways in cancer (hsa05200)
  Rheumatoid arthritis (hsa05323)
• Reactome Pathway:
  Signaling by ROBO receptors (R-HSA-376176)
  Chemokine receptors bind chemokines (R-HSA-380108)
  G alpha (i) signalling events (R-HSA-418594)
  Estrogen-dependent gene expression (R-HSA-9018519)
  Nuclear signaling by ERBB4 (R-HSA-1251985)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Stromal cell-derived factor 1 (CXCL12).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Stromal cell-derived factor 1 (CXCL12).	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Stromal cell-derived factor 1 (CXCL12).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Stromal cell-derived factor 1 (CXCL12).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Stromal cell-derived factor 1 (CXCL12).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Stromal cell-derived factor 1 (CXCL12).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Stromal cell-derived factor 1 (CXCL12).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Stromal cell-derived factor 1 (CXCL12).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Stromal cell-derived factor 1 (CXCL12).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Stromal cell-derived factor 1 (CXCL12).	[9]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Stromal cell-derived factor 1 (CXCL12).	[10]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Stromal cell-derived factor 1 (CXCL12).	[5]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Stromal cell-derived factor 1 (CXCL12).	[11]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Stromal cell-derived factor 1 (CXCL12).	[12]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Stromal cell-derived factor 1 (CXCL12).	[13]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Stromal cell-derived factor 1 (CXCL12).	[14]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Stromal cell-derived factor 1 (CXCL12).	[11]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of Stromal cell-derived factor 1 (CXCL12).	[16]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Stromal cell-derived factor 1 (CXCL12).	[17]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Stromal cell-derived factor 1 (CXCL12).	[18]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Stromal cell-derived factor 1 (CXCL12).	[19]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Stromal cell-derived factor 1 (CXCL12).	[20]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Stromal cell-derived factor 1 (CXCL12).	[16]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Stromal cell-derived factor 1 (CXCL12).	[21]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Stromal cell-derived factor 1 (CXCL12).	[22]
Ritonavir	DMU764S	Approved	Ritonavir decreases the expression of Stromal cell-derived factor 1 (CXCL12).	[23]
Estrone	DM5T6US	Approved	Estrone increases the expression of Stromal cell-derived factor 1 (CXCL12).	[11]
Ardeparin	DMYRX8B	Approved	Ardeparin decreases the expression of Stromal cell-derived factor 1 (CXCL12).	[24]
Propofol	DMB4OLE	Approved	Propofol decreases the expression of Stromal cell-derived factor 1 (CXCL12).	[25]
Sevoflurane	DMC9O43	Approved	Sevoflurane increases the expression of Stromal cell-derived factor 1 (CXCL12).	[25]
Mestranol	DMG3F94	Approved	Mestranol increases the expression of Stromal cell-derived factor 1 (CXCL12).	[11]
Cetrorelix	DMFD9Q6	Approved	Cetrorelix decreases the expression of Stromal cell-derived factor 1 (CXCL12).	[26]
Plerixafor	DMCJN1P	Approved	Plerixafor decreases the expression of Stromal cell-derived factor 1 (CXCL12).	[27]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone decreases the expression of Stromal cell-derived factor 1 (CXCL12).	[29]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Stromal cell-derived factor 1 (CXCL12).	[5]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Stromal cell-derived factor 1 (CXCL12).	[30]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Stromal cell-derived factor 1 (CXCL12).	[31]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Stromal cell-derived factor 1 (CXCL12).	[32]
Calcium phosphate	DMGXCY9	Phase 2	Calcium phosphate increases the expression of Stromal cell-derived factor 1 (CXCL12).	[33]
HEXESTROL	DM9AGWQ	Withdrawn from market	HEXESTROL increases the expression of Stromal cell-derived factor 1 (CXCL12).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Stromal cell-derived factor 1 (CXCL12).	[35]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Stromal cell-derived factor 1 (CXCL12).	[8]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Stromal cell-derived factor 1 (CXCL12).	[36]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Stromal cell-derived factor 1 (CXCL12).	[4]
Daidzein	DMRFTJX	Investigative	Daidzein increases the expression of Stromal cell-derived factor 1 (CXCL12).	[35]
Apigenin	DMI3491	Investigative	Apigenin increases the expression of Stromal cell-derived factor 1 (CXCL12).	[35]
Benzoquinone	DMNBA0G	Investigative	Benzoquinone increases the expression of Stromal cell-derived factor 1 (CXCL12).	[14]
27-hydroxycholesterol	DM2L6OZ	Investigative	27-hydroxycholesterol increases the expression of Stromal cell-derived factor 1 (CXCL12).	[38]
Fibrates	DMFNTMY	Investigative	Fibrates decreases the expression of Stromal cell-derived factor 1 (CXCL12).	[39]
HPTE	DMRPZD4	Investigative	HPTE increases the expression of Stromal cell-derived factor 1 (CXCL12).	[31]
LIQUIRTIGENIN	DM6YSG3	Investigative	LIQUIRTIGENIN increases the expression of Stromal cell-derived factor 1 (CXCL12).	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the response to substance of Stromal cell-derived factor 1 (CXCL12).	[15]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the response to substance of Stromal cell-derived factor 1 (CXCL12).	[15]
Fosfosal	DMDIC39	Approved	Fosfosal affects the binding of Stromal cell-derived factor 1 (CXCL12).	[28]
Telmisartan	DMS3GX2	Phase 3 Trial	Telmisartan decreases the response to substance of Stromal cell-derived factor 1 (CXCL12).	[15]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the secretion of Stromal cell-derived factor 1 (CXCL12).	[37]
GW1929	DMOV980	Investigative	GW1929 decreases the response to substance of Stromal cell-derived factor 1 (CXCL12).	[15]

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