Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0ECWK3)

• DOT Name: Thrombospondin-1 (THBS1)
• Synonyms: Glycoprotein G
• Gene Name: THBS1
• UniProt ID: TSP1_HUMAN
• PDB ID: 1LSL; 1UX6; 1Z78; 1ZA4; 2ERF; 2ES3; 2OUH; 2OUJ; 3R6B; 5FOE; 7YYK
• Pfam ID: PF12947 ; PF00090 ; PF02412 ; PF05735 ; PF00093
• Sequence:
  MGLAWGLGVLFLMHVCGTNRIPESGGDNSVFDIFELTGAARKGSGRRLVKGPDPSSPAFR
  IEDANLIPPVPDDKFQDLVDAVRAEKGFLLLASLRQMKKTRGTLLALERKDHSGQVFSVV
  SNGKAGTLDLSLTVQGKQHVVSVEEALLATGQWKSITLFVQEDRAQLYIDCEKMENAELD
  VPIQSVFTRDLASIARLRIAKGGVNDNFQGVLQNVRFVFGTTPEDILRNKGCSSSTSVLL
  TLDNNVVNGSSPAIRTNYIGHKTKDLQAICGISCDELSSMVLELRGLRTIVTTLQDSIRK
  VTEENKELANELRRPPLCYHNGVQYRNNEEWTVDSCTECHCQNSVTICKKVSCPIMPCSN
  ATVPDGECCPRCWPSDSADDGWSPWSEWTSCSTSCGNGIQQRGRSCDSLNNRCEGSSVQT
  RTCHIQECDKRFKQDGGWSHWSPWSSCSVTCGDGVITRIRLCNSPSPQMNGKPCEGEARE
  TKACKKDACPINGGWGPWSPWDICSVTCGGGVQKRSRLCNNPTPQFGGKDCVGDVTENQI
  CNKQDCPIDGCLSNPCFAGVKCTSYPDGSWKCGACPPGYSGNGIQCTDVDECKEVPDACF
  NHNGEHRCENTDPGYNCLPCPPRFTGSQPFGQGVEHATANKQVCKPRNPCTDGTHDCNKN
  AKCNYLGHYSDPMYRCECKPGYAGNGIICGEDTDLDGWPNENLVCVANATYHCKKDNCPN
  LPNSGQEDYDKDGIGDACDDDDDNDKIPDDRDNCPFHYNPAQYDYDRDDVGDRCDNCPYN
  HNPDQADTDNNGEGDACAADIDGDGILNERDNCQYVYNVDQRDTDMDGVGDQCDNCPLEH
  NPDQLDSDSDRIGDTCDNNQDIDEDGHQNNLDNCPYVPNANQADHDKDGKGDACDHDDDN
  DGIPDDKDNCRLVPNPDQKDSDGDGRGDACKDDFDHDSVPDIDDICPENVDISETDFRRF
  QMIPLDPKGTSQNDPNWVVRHQGKELVQTVNCDPGLAVGYDEFNAVDFSGTFFINTERDD
  DYAGFVFGYQSSSRFYVVMWKQVTQSYWDTNPTRAQGYSGLSVKVVNSTTGPGEHLRNAL
  WHTGNTPGQVRTLWHDPRHIGWKDFTAYRWRLSHRPKTGFIRVVMYEGKKIMADSGPIYD
  KTYAGGRLGLFVFSQEMVFFSDLKYECRDP
• Function: Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. Multifunctional, involved in inflammation, angiogenesis, wound healing, reactive oxygen species (ROS) signaling, nitrous oxide (NO) signaling, apoptosis, senescence, aging, cellular self-renewal, stemness, and cardiovascular and metabolic homeostasis. Negatively modulates dendritic cell activation and cytokine release, as part of an autocrine feedback loop, contributing to the resolution of inflammation and immune homeostasis. Ligand for receptor CD47. Modulates nitrous oxide (NO) signaling via CD47, hence playing a role as a pressor agent, supporting blood pressure. Plays a role in endothelial cell senescence, acting via CD47, by increasing the abundance and activation of NADPH oxidase NOX1, and so generating excess ROS. Inhibits stem cell self-renewal, acting via CD47 signaling, probably by regulation of the stem cell transcription factors POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4. Negatively modulates wound healing, acting via CD47. Ligand for receptor CD36. Involved in inducing apoptosis in podocytes in response to elevated free fatty acids, acting via CD36. Plays a role in suppressing angiogenesis, acting, depending on context, via CD36 or CD47. Promotes cellular senescence in a TP53-CDKN1A-RB1 signaling-dependent manner. Ligand for immunoglobulin-like cell surface receptor SIRPA. Involved in ROS signaling in non-phagocytic cells, stimulating NADPH oxidase-derived ROS production, acting via interaction with SIRPA. Plays a role in metabolic dysfunction in diet-induced obesity, perhaps acting by exacerbating adipose inflammatory activity; its effects may be mediated, at least in part, through enhanced adipocyte proliferation. Plays a role in ER stress response, via its interaction with the activating transcription factor 6 alpha (ATF6) which produces adaptive ER stress response factors. May be involved in age-related conditions, including metabolic dysregulation, during normal aging.
• Tissue Specificity: Expressed by platelets (at protein level) . Expressed by monocyte-derived immature and mature dendritic cells (at protein level) .
• KEGG Pathway:
  Rap1 sig.ling pathway (hsa04015)
  p53 sig.ling pathway (hsa04115)
  Phagosome (hsa04145)
  Efferocytosis (hsa04148)
  PI3K-Akt sig.ling pathway (hsa04151)
  TGF-beta sig.ling pathway (hsa04350)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Cytoskeleton in muscle cells (hsa04820)
  Malaria (hsa05144)
  Human papillomavirus infection (hsa05165)
  Proteoglycans in cancer (hsa05205)
  MicroR.s in cancer (hsa05206)
  Bladder cancer (hsa05219)
• Reactome Pathway:
  Signaling by PDGF (R-HSA-186797)
  Integrin cell surface interactions (R-HSA-216083)
  Syndecan interactions (R-HSA-3000170)
  Defective B3GALTL causes PpS (R-HSA-5083635)
  O-glycosylation of TSR domain-containing proteins (R-HSA-5173214)
  RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function (R-HSA-8936459)
  Platelet degranulation (R-HSA-114608)

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
Irinotecan	DMP6SC2	Approved	Thrombospondin-1 (THBS1) decreases the response to substance of Irinotecan.	[53]

56 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 Thrombospondin-1 (THBS1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Thrombospondin-1 (THBS1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Thrombospondin-1 (THBS1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Thrombospondin-1 (THBS1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Thrombospondin-1 (THBS1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Thrombospondin-1 (THBS1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Thrombospondin-1 (THBS1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Thrombospondin-1 (THBS1).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Thrombospondin-1 (THBS1).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Thrombospondin-1 (THBS1).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Thrombospondin-1 (THBS1).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Thrombospondin-1 (THBS1).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Thrombospondin-1 (THBS1).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Thrombospondin-1 (THBS1).	[14]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Thrombospondin-1 (THBS1).	[15]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Thrombospondin-1 (THBS1).	[16]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Thrombospondin-1 (THBS1).	[17]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Thrombospondin-1 (THBS1).	[18]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Thrombospondin-1 (THBS1).	[19]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Thrombospondin-1 (THBS1).	[20]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Thrombospondin-1 (THBS1).	[21]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Thrombospondin-1 (THBS1).	[3]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Thrombospondin-1 (THBS1).	[22]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Thrombospondin-1 (THBS1).	[23]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Thrombospondin-1 (THBS1).	[24]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Thrombospondin-1 (THBS1).	[25]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Thrombospondin-1 (THBS1).	[26]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Thrombospondin-1 (THBS1).	[27]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Thrombospondin-1 (THBS1).	[28]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Thrombospondin-1 (THBS1).	[3]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Thrombospondin-1 (THBS1).	[29]
Prednisolone	DMQ8FR2	Approved	Prednisolone increases the expression of Thrombospondin-1 (THBS1).	[30]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone increases the expression of Thrombospondin-1 (THBS1).	[30]
Busulfan	DMXYJ9C	Approved	Busulfan increases the expression of Thrombospondin-1 (THBS1).	[31]
Clopidogrel	DMOL54H	Approved	Clopidogrel increases the expression of Thrombospondin-1 (THBS1).	[32]
Magnesium	DMU4ORS	Approved	Magnesium increases the expression of Thrombospondin-1 (THBS1).	[33]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Thrombospondin-1 (THBS1).	[34]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin decreases the expression of Thrombospondin-1 (THBS1).	[5]
Atorvastatin	DMF28YC	Phase 3 Trial	Atorvastatin decreases the expression of Thrombospondin-1 (THBS1).	[35]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Thrombospondin-1 (THBS1).	[36]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Thrombospondin-1 (THBS1).	[38]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Thrombospondin-1 (THBS1).	[39]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Thrombospondin-1 (THBS1).	[40]
Scriptaid	DM9JZ21	Preclinical	Scriptaid affects the expression of Thrombospondin-1 (THBS1).	[41]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Thrombospondin-1 (THBS1).	[1]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Thrombospondin-1 (THBS1).	[43]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Thrombospondin-1 (THBS1).	[44]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Thrombospondin-1 (THBS1).	[45]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Thrombospondin-1 (THBS1).	[46]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Thrombospondin-1 (THBS1).	[47]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Thrombospondin-1 (THBS1).	[48]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone increases the expression of Thrombospondin-1 (THBS1).	[49]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid decreases the expression of Thrombospondin-1 (THBS1).	[3]
I-BET151	DMYRUH2	Investigative	I-BET151 decreases the expression of Thrombospondin-1 (THBS1).	[50]
NORCANTHARIDIN	DM9B6Y1	Investigative	NORCANTHARIDIN increases the expression of Thrombospondin-1 (THBS1).	[51]
PFI-1	DMVFK3J	Investigative	PFI-1 decreases the expression of Thrombospondin-1 (THBS1).	[50]

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 decreases the methylation of Thrombospondin-1 (THBS1).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Thrombospondin-1 (THBS1).	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
adenosine diphosphate	DMFUHKP	Investigative	adenosine diphosphate increases the secretion of Thrombospondin-1 (THBS1).	[52]

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