Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTISPT4X)

• DOT Name: Transcription factor Sp1 (SP1)
• Gene Name: SP1
• UniProt ID: SP1_HUMAN
• PDB ID: 1SP1; 1SP2; 1VA1; 1VA2; 1VA3; 6PV0; 6PV1; 6PV2; 6PV3; 6UCO; 6UCP
• Pfam ID: PF00096
• Sequence:
  MSDQDHSMDEMTAVVKIEKGVGGNNGGNGNGGGAFSQARSSSTGSSSSTGGGGQESQPSP
  LALLAATCSRIESPNENSNNSQGPSQSGGTGELDLTATQLSQGANGWQIISSSSGATPTS
  KEQSGSSTNGSNGSESSKNRTVSGGQYVVAAAPNLQNQQVLTGLPGVMPNIQYQVIPQFQ
  TVDGQQLQFAATGAQVQQDGSGQIQIIPGANQQIITNRGSGGNIIAAMPNLLQQAVPLQG
  LANNVLSGQTQYVTNVPVALNGNITLLPVNSVSAATLTPSSQAVTISSSGSQESGSQPVT
  SGTTISSASLVSSQASSSSFFTNANSYSTTTTTSNMGIMNFTTSGSSGTNSQGQTPQRVS
  GLQGSDALNIQQNQTSGGSLQAGQQKEGEQNQQTQQQQILIQPQLVQGGQALQALQAAPL
  SGQTFTTQAISQETLQNLQLQAVPNSGPIIIRTPTVGPNGQVSWQTLQLQNLQVQNPQAQ
  TITLAPMQGVSLGQTSSSNTTLTPIASAASIPAGTVTVNAAQLSSMPGLQTINLSALGTS
  GIQVHPIQGLPLAIANAPGDHGAQLGLHGAGGDGIHDDTAGGEEGENSPDAQPQAGRRTR
  REACTCPYCKDSEGRGSGDPGKKKQHICHIQGCGKVYGKTSHLRAHLRWHTGERPFMCTW
  SYCGKRFTRSDELQRHKRTHTGEKKFACPECPKRFMRSDHLSKHIKTHQNKKGGPGVALS
  VGTLPLDSGAGSEGSGTATPSALITTNMVAMEAICPEGIARLANSGINVMQVADLQSINI
  SGNGF
• Function: Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. Binds with high affinity to GC-rich motifs and regulates the expression of a large number of genes involved in a variety of processes such as cell growth, apoptosis, differentiation and immune responses. Highly regulated by post-translational modifications (phosphorylations, sumoylation, proteolytic cleavage, glycosylation and acetylation). Binds also the PDGFR-alpha G-box promoter. May have a role in modulating the cellular response to DNA damage. Implicated in chromatin remodeling. Plays an essential role in the regulation of FE65 gene expression. In complex with ATF7IP, maintains telomerase activity in cancer cells by inducing TERT and TERC gene expression. Isoform 3 is a stronger activator of transcription than isoform 1. Positively regulates the transcription of the core clock component BMAL1. Plays a role in the recruitment of SMARCA4/BRG1 on the c-FOS promoter. Plays a role in protecting cells against oxidative stress following brain injury by regulating the expression of RNF112.
• Tissue Specificity: Up-regulated in adenocarcinomas of the stomach (at protein level). Isoform 3 is ubiquitously expressed at low levels.
• KEGG Pathway:
  Endocrine resistance (hsa01522)
  Mitophagy - animal (hsa04137)
  TGF-beta sig.ling pathway (hsa04350)
  Estrogen sig.ling pathway (hsa04915)
  Cortisol synthesis and secretion (hsa04927)
  Parathyroid hormone synthesis, secretion and action (hsa04928)
  Cushing syndrome (hsa04934)
  Huntington disease (hsa05016)
  Spinocerebellar ataxia (hsa05017)
  Human cytomegalovirus infection (hsa05163)
  Pathways in cancer (hsa05200)
  Transcriptio.l misregulation in cancer (hsa05202)
  Breast cancer (hsa05224)
  Choline metabolism in cancer (hsa05231)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  SMAD2/SMAD3 (R-HSA-2173796)
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)
  Oncogene Induced Senescence (R-HSA-2559585)
  RNA polymerase II transcribes snRNA genes (R-HSA-6807505)
  Estrogen-dependent gene expression (R-HSA-9018519)
  SARS-CoV-1 targets host intracellular signalling and regulatory pathways (R-HSA-9735871)
  Regulation of CDH11 gene transcription (R-HSA-9762293)
  NFE2L2 regulating tumorigenic genes (R-HSA-9818030)
  PPARA activates gene expression (R-HSA-1989781)

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
Fructose	DM43AN2	Approved	Transcription factor Sp1 (SP1) increases the Metabolism and nutrition disorders ADR of Fructose.	[51]

55 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 Transcription factor Sp1 (SP1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transcription factor Sp1 (SP1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcription factor Sp1 (SP1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transcription factor Sp1 (SP1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transcription factor Sp1 (SP1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transcription factor Sp1 (SP1).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Transcription factor Sp1 (SP1).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Transcription factor Sp1 (SP1).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Transcription factor Sp1 (SP1).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Transcription factor Sp1 (SP1).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Transcription factor Sp1 (SP1).	[10]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Transcription factor Sp1 (SP1).	[11]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Transcription factor Sp1 (SP1).	[12]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Transcription factor Sp1 (SP1).	[12]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Transcription factor Sp1 (SP1).	[14]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the activity of Transcription factor Sp1 (SP1).	[15]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Transcription factor Sp1 (SP1).	[16]
Daunorubicin	DMQUSBT	Approved	Daunorubicin decreases the expression of Transcription factor Sp1 (SP1).	[18]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Transcription factor Sp1 (SP1).	[19]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the activity of Transcription factor Sp1 (SP1).	[20]
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the expression of Transcription factor Sp1 (SP1).	[21]
Artesunate	DMR27C8	Approved	Artesunate decreases the expression of Transcription factor Sp1 (SP1).	[22]
Glutathione	DMAHMT9	Approved	Glutathione decreases the expression of Transcription factor Sp1 (SP1).	[23]
Penicillamine	DM40EF6	Approved	Penicillamine increases the expression of Transcription factor Sp1 (SP1).	[5]
Promegestone	DMK4S8I	Approved	Promegestone increases the expression of Transcription factor Sp1 (SP1).	[24]
Plicamycin	DM7C8YV	Approved	Plicamycin decreases the expression of Transcription factor Sp1 (SP1).	[25]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Transcription factor Sp1 (SP1).	[26]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Transcription factor Sp1 (SP1).	[28]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin increases the expression of Transcription factor Sp1 (SP1).	[29]
Coprexa	DMA0WEK	Phase 3	Coprexa increases the expression of Transcription factor Sp1 (SP1).	[5]
I3C	DMIGFOR	Phase 3	I3C decreases the activity of Transcription factor Sp1 (SP1).	[30]
Genistein	DM0JETC	Phase 2/3	Genistein increases the activity of Transcription factor Sp1 (SP1).	[31]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the activity of Transcription factor Sp1 (SP1).	[32]
R-roscovitine	DMSH108	Phase 2	R-roscovitine increases the expression of Transcription factor Sp1 (SP1).	[33]
Pelitinib	DMIW453	Phase 2	Pelitinib decreases the activity of Transcription factor Sp1 (SP1).	[34]
UCN-01	DMUNJZB	Phase 2	UCN-01 increases the expression of Transcription factor Sp1 (SP1).	[33]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the activity of Transcription factor Sp1 (SP1).	[35]
Olomoucine	DMNAFG1	Terminated	Olomoucine increases the expression of Transcription factor Sp1 (SP1).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transcription factor Sp1 (SP1).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the activity of Transcription factor Sp1 (SP1).	[38]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Transcription factor Sp1 (SP1).	[39]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Transcription factor Sp1 (SP1).	[40]
AHPN	DM8G6O4	Investigative	AHPN increases the expression of Transcription factor Sp1 (SP1).	[41]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the expression of Transcription factor Sp1 (SP1).	[42]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos increases the expression of Transcription factor Sp1 (SP1).	[43]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR decreases the expression of Transcription factor Sp1 (SP1).	[44]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate increases the expression of Transcription factor Sp1 (SP1).	[45]
Cordycepin	DM72Y01	Investigative	Cordycepin decreases the expression of Transcription factor Sp1 (SP1).	[46]
Lead acetate	DML0GZ2	Investigative	Lead acetate increases the expression of Transcription factor Sp1 (SP1).	[47]
CATECHIN	DMY38SB	Investigative	CATECHIN increases the expression of Transcription factor Sp1 (SP1).	[48]
2-tert-butylbenzene-1,4-diol	DMNXI1E	Investigative	2-tert-butylbenzene-1,4-diol increases the expression of Transcription factor Sp1 (SP1).	[44]
15-deoxy-Delta(12, 14)-prostaglandin J(2)	DM8VUX3	Investigative	15-deoxy-Delta(12, 14)-prostaglandin J(2) decreases the expression of Transcription factor Sp1 (SP1).	[12]
Buthionine sulfoximine	DMJ46CB	Investigative	Buthionine sulfoximine increases the activity of Transcription factor Sp1 (SP1).	[49]
Nitrosoglutathione	DMZ9WI4	Investigative	Nitrosoglutathione increases the activity of Transcription factor Sp1 (SP1).	[50]
Bisindolylmaleimide-I	DMOQJZC	Investigative	Bisindolylmaleimide-I increases the expression of Transcription factor Sp1 (SP1).	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Etoposide increases the phosphorylation of Transcription factor Sp1 (SP1).	[13]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the acetylation of Transcription factor Sp1 (SP1).	[27]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Transcription factor Sp1 (SP1).	[36]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Transcription factor Sp1 (SP1).	[37]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Transcription factor Sp1 (SP1).	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Capsaicin	DMGMF6V	Approved	Capsaicin increases the localization of Transcription factor Sp1 (SP1).	[17]

References

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