Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL8QJDX)

• DOT Name: Histone acetyltransferase p300 (EP300)
• Synonyms: p300 HAT; EC 2.3.1.48; E1A-associated protein p300; Histone butyryltransferase p300; EC 2.3.1.-; Histone crotonyltransferase p300; EC 2.3.1.-; Protein 2-hydroxyisobutyryltransferase p300; EC 2.3.1.-; Protein lactyltransferas p300; EC 2.3.1.-; Protein propionyltransferase p300; EC 2.3.1.-
• Gene Name: EP300
• Related Disease:
  Rubinstein-Taybi syndrome
  Rubinstein-Taybi syndrome due to EP300 haploinsufficiency
• UniProt ID: EP300_HUMAN
• PDB ID: 1L3E ; 1P4Q ; 2K8F ; 2MH0 ; 2MZD ; 3BIY ; 3I3J ; 3IO2 ; 3P57 ; 3T92 ; 4BHW ; 4PZR ; 4PZS ; 4PZT ; 5BT3 ; 5KJ2 ; 5LKT ; 5LKU ; 5LKX ; 5LKZ ; 5LPK ; 5LPM ; 5NU5 ; 5XZC ; 6DS6 ; 6FGN ; 6FGS ; 6GYR ; 6GYT ; 6K4N ; 6PF1 ; 6PGU ; 6V8B ; 6V8K ; 6V8N ; 6V90 ; 7LJE ; 7QGS ; 7SS8 ; 7SSK ; 7SZQ ; 7UGI ; 7VHY ; 7VHZ ; 7VI0 ; 7W9V ; 7XEZ ; 7XFG ; 8E1D ; 8GZC ; 8HAG ; 8HAH ; 8HAI ; 8HAJ ; 8HAK
• EC Number: 2.3.1.-; 2.3.1.48
• Pfam ID: PF00439 ; PF09030 ; PF08214 ; PF02172 ; PF06001 ; PF02135 ; PF00569
• Sequence:
  MAENVVEPGPPSAKRPKLSSPALSASASDGTDFGSLFDLEHDLPDELINSTELGLTNGGD
  INQLQTSLGMVQDAASKHKQLSELLRSGSSPNLNMGVGGPGQVMASQAQQSSPGLGLINS
  MVKSPMTQAGLTSPNMGMGTSGPNQGPTQSTGMMNSPVNQPAMGMNTGMNAGMNPGMLAA
  GNGQGIMPNQVMNGSIGAGRGRQNMQYPNPGMGSAGNLLTEPLQQGSPQMGGQTGLRGPQ
  PLKMGMMNNPNPYGSPYTQNPGQQIGASGLGLQIQTKTVLSNNLSPFAMDKKAVPGGGMP
  NMGQQPAPQVQQPGLVTPVAQGMGSGAHTADPEKRKLIQQQLVLLLHAHKCQRREQANGE
  VRQCNLPHCRTMKNVLNHMTHCQSGKSCQVAHCASSRQIISHWKNCTRHDCPVCLPLKNA
  GDKRNQQPILTGAPVGLGNPSSLGVGQQSAPNLSTVSQIDPSSIERAYAALGLPYQVNQM
  PTQPQVQAKNQQNQQPGQSPQGMRPMSNMSASPMGVNGGVGVQTPSLLSDSMLHSAINSQ
  NPMMSENASVPSLGPMPTAAQPSTTGIRKQWHEDITQDLRNHLVHKLVQAIFPTPDPAAL
  KDRRMENLVAYARKVEGDMYESANNRAEYYHLLAEKIYKIQKELEEKRRTRLQKQNMLPN
  AAGMVPVSMNPGPNMGQPQPGMTSNGPLPDPSMIRGSVPNQMMPRITPQSGLNQFGQMSM
  AQPPIVPRQTPPLQHHGQLAQPGALNPPMGYGPRMQQPSNQGQFLPQTQFPSQGMNVTNI
  PLAPSSGQAPVSQAQMSSSSCPVNSPIMPPGSQGSHIHCPQLPQPALHQNSPSPVPSRTP
  TPHHTPPSIGAQQPPATTIPAPVPTPPAMPPGPQSQALHPPPRQTPTPPTTQLPQQVQPS
  LPAAPSADQPQQQPRSQQSTAASVPTPTAPLLPPQPATPLSQPAVSIEGQVSNPPSTSST
  EVNSQAIAEKQPSQEVKMEAKMEVDQPEPADTQPEDISESKVEDCKMESTETEERSTELK
  TEIKEEEDQPSTSATQSSPAPGQSKKKIFKPEELRQALMPTLEALYRQDPESLPFRQPVD
  PQLLGIPDYFDIVKSPMDLSTIKRKLDTGQYQEPWQYVDDIWLMFNNAWLYNRKTSRVYK
  YCSKLSEVFEQEIDPVMQSLGYCCGRKLEFSPQTLCCYGKQLCTIPRDATYYSYQNRYHF
  CEKCFNEIQGESVSLGDDPSQPQTTINKEQFSKRKNDTLDPELFVECTECGRKMHQICVL
  HHEIIWPAGFVCDGCLKKSARTRKENKFSAKRLPSTRLGTFLENRVNDFLRRQNHPESGE
  VTVRVVHASDKTVEVKPGMKARFVDSGEMAESFPYRTKALFAFEEIDGVDLCFFGMHVQE
  YGSDCPPPNQRRVYISYLDSVHFFRPKCLRTAVYHEILIGYLEYVKKLGYTTGHIWACPP
  SEGDDYIFHCHPPDQKIPKPKRLQEWYKKMLDKAVSERIVHDYKDIFKQATEDRLTSAKE
  LPYFEGDFWPNVLEESIKELEQEEEERKREENTSNESTDVTKGDSKNAKKKNNKKTSKNK
  SSLSRGNKKKPGMPNVSNDLSQKLYATMEKHKEVFFVIRLIAGPAANSLPPIVDPDPLIP
  CDLMDGRDAFLTLARDKHLEFSSLRRAQWSTMCMLVELHTQSQDRFVYTCNECKHHVETR
  WHCTVCEDYDLCITCYNTKNHDHKMEKLGLGLDDESNNQQAAATQSPGDSRRLSIQRCIQ
  SLVHACQCRNANCSLPSCQKMKRVVQHTKGCKRKTNGGCPICKQLIALCCYHAKHCQENK
  CPVPFCLNIKQKLRQQQLQHRLQQAQMLRRRMASMQRTGVVGQQQGLPSPTPATPTTPTG
  QQPTTPQTPQPTSQPQPTPPNSMPPYLPRTQAAGPVSQGKAAGQVTPPTPPQTAQPPLPG
  PPPAAVEMAMQIQRAAETQRQMAHVQIFQRPIQHQMPPMTPMAPMGMNPPPMTRGPSGHL
  EPGMGPTGMQQQPPWSQGGLPQPQQLQSGMPRPAMMSVAQHGQPLNMAPQPGLGQVGISP
  LKPGTVSQQALQNLLRTLRSPSSPLQQQQVLSILHANPQLLAAFIKQRAAKYANSNPQPI
  PGQPGMPQGQPGLQPPTMPGQQGVHSNPAMQNMNPMQAGVQRAGLPQQQPQQQLQPPMGG
  MSPQAQQMNMNHNTMPSQFRDILRRQQMMQQQQQQGAGPGIGPGMANHNQFQQPQGVGYP
  PQQQQRMQHHMQQMQQGNMGQIGQLPQALGAEAGASLQAYQQRLLQQQMGSPVQPNPMSP
  QQHMLPNQAQSPHLQGQQIPNSLSNQVRSPQPVPSPRPQSQPPHSSPSPRMQPQPSPHHV
  SPQTSSPHPGLVAAQANPMEQGHFASPDQNSMLSQLASNPGMANLHGASATDLGLSTDNS
  DLNSNLSQSTLDIH
• Function: Functions as a histone acetyltransferase and regulates transcription via chromatin remodeling. Acetylates all four core histones in nucleosomes. Histone acetylation gives an epigenetic tag for transcriptional activation. Mediates acetylation of histone H3 at 'Lys-122' (H3K122ac), a modification that localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability. Mediates acetylation of histone H3 at 'Lys-18' and 'Lys-27' (H3K18ac and H3K27ac, respectively). Also able to acetylate histone lysine residues that are already monomethylated on the same side chain to form N6-acetyl-N6-methyllysine (Kacme), an epigenetic mark of active chromatin associated with increased transcriptional initiation. Catalyzes formation of histone H4 acetyl-methylated at 'Lys-5' and 'Lys-12' (H4K5acme and H4K12acme, respectively). Also functions as acetyltransferase for non-histone targets, such as ALX1, HDAC1, PRMT1, SIRT2 or STAT3. Acetylates 'Lys-131' of ALX1 and acts as its coactivator. Acetylates SIRT2 and is proposed to indirectly increase the transcriptional activity of p53/TP53 through acetylation and subsequent attenuation of SIRT2 deacetylase function. Following DNA damage, forms a stress-responsive p53/TP53 coactivator complex with JMY which mediates p53/TP53 acetylation, thereby increasing p53/TP53-dependent transcription and apoptosis. Promotes chromatin acetylation in heat shock responsive HSP genes during the heat shock response (HSR), thereby stimulating HSR transcription. Acetylates HDAC1 leading to its inactivation and modulation of transcription. Acetylates 'Lys-247' of EGR2. Acts as a TFAP2A-mediated transcriptional coactivator in presence of CITED2. Plays a role as a coactivator of NEUROD1-dependent transcription of the secretin and p21 genes and controls terminal differentiation of cells in the intestinal epithelium. Promotes cardiac myocyte enlargement. Can also mediate transcriptional repression. Acetylates FOXO1 and enhances its transcriptional activity. Acetylates STAT3 at different sites, promoting both STAT3 dimerization and activation and recruitment to chromatin. Acetylates BCL6 wich disrupts its ability to recruit histone deacetylases and hinders its transcriptional repressor activity. Participates in CLOCK or NPAS2-regulated rhythmic gene transcription; exhibits a circadian association with CLOCK or NPAS2, correlating with increase in PER1/2 mRNA and histone H3 acetylation on the PER1/2 promoter. Acetylates MTA1 at 'Lys-626' which is essential for its transcriptional coactivator activity. Acetylates XBP1 isoform 2; acetylation increases protein stability of XBP1 isoform 2 and enhances its transcriptional activity. Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER). Acetylates MEF2D. Acetylates and stabilizes ZBTB7B protein by antagonizing ubiquitin conjugation and degradation, this mechanism may be involved in CD4/CD8 lineage differentiation. Acetylates GABPB1, impairing GABPB1 heterotetramerization and activity. Acetylates PCK1 and promotes PCK1 anaplerotic activity. Acetylates RXRA and RXRG. Acetylates isoform M2 of PKM (PKM2), promoting its homodimerization and conversion into a protein kinase. Acetylates RPTOR in response to leucine, leading to activation of the mTORC1 complex. Mediates cAMP-gene regulation by binding specifically to phosphorylated CREBBP. In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as (2E)-butenoyl-CoA (crotonyl-CoA), butanoyl-CoA (butyryl-CoA), 2-hydroxyisobutanoyl-CoA (2-hydroxyisobutyryl-CoA), lactoyl-CoA or propanoyl-CoA (propionyl-CoA), and is able to mediate protein crotonylation, butyrylation, 2-hydroxyisobutyrylation, lactylation or propionylation, respectively. Acts as a histone crotonyltransferase; crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. Histone crotonyltransferase activity is dependent on the concentration of (2E)-butenoyl-CoA (crotonyl-CoA) substrate and such activity is weak when (2E)-butenoyl-CoA (crotonyl-CoA) concentration is low. Also acts as a histone butyryltransferase; butyrylation marks active promoters. Catalyzes histone lactylation in macrophages by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription. Acts as a protein-lysine 2-hydroxyisobutyryltransferase; regulates glycolysis by mediating 2-hydroxyisobutyrylation of glycolytic enzymes. Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway ; (Microbial infection) In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein.
• KEGG Pathway:
  Polycomb repressive complex (hsa03083)
  Viral life cycle - HIV-1 (hsa03250)
  cAMP sig.ling pathway (hsa04024)
  HIF-1 sig.ling pathway (hsa04066)
  FoxO sig.ling pathway (hsa04068)
  Cell cycle (hsa04110)
  Wnt sig.ling pathway (hsa04310)
  Notch sig.ling pathway (hsa04330)
  TGF-beta sig.ling pathway (hsa04350)
  Adherens junction (hsa04520)
  JAK-STAT sig.ling pathway (hsa04630)
  Long-term potentiation (hsa04720)
  Melanogenesis (hsa04916)
  Thyroid hormone sig.ling pathway (hsa04919)
  Glucagon sig.ling pathway (hsa04922)
  Growth hormone synthesis, secretion and action (hsa04935)
  Huntington disease (hsa05016)
  Tuberculosis (hsa05152)
  Hepatitis B (hsa05161)
  Influenza A (hsa05164)
  Human papillomavirus infection (hsa05165)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Pathways in cancer (hsa05200)
  Viral carcinogenesis (hsa05203)
  MicroR.s in cancer (hsa05206)
  Re.l cell carcinoma (hsa05211)
  Prostate cancer (hsa05215)
• Reactome Pathway:
  RORA activates gene expression (R-HSA-1368082)
  Polo-like kinase mediated events (R-HSA-156711)
  Pre-NOTCH Transcription and Translation (R-HSA-1912408)
  PPARA activates gene expression (R-HSA-1989781)
  Formation of the beta-catenin (R-HSA-201722)
  Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells (R-HSA-210744)
  NOTCH1 Intracellular Domain Regulates Transcription (R-HSA-2122947)
  SMAD2/SMAD3 (R-HSA-2173796)
  NOTCH2 intracellular domain regulates transcription (R-HSA-2197563)
  Constitutive Signaling by NOTCH1 PEST Domain Mutants (R-HSA-2644606)
  Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants (R-HSA-2894862)
  LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production (R-HSA-3134973)
  HATs acetylate histones (R-HSA-3214847)
  Attenuation phase (R-HSA-3371568)
  Transcriptional regulation of white adipocyte differentiation (R-HSA-381340)
  SUMOylation of transcription cofactors (R-HSA-3899300)
  Circadian Clock (R-HSA-400253)
  B-WICH complex positively regulates rRNA expression (R-HSA-5250924)
  Activation of anterior HOX genes in hindbrain development during early embryogenesis (R-HSA-5617472)
  CD209 (DC-SIGN) signaling (R-HSA-5621575)
  Metalloprotease DUBs (R-HSA-5689901)
  Formation of TC-NER Pre-Incision Complex (R-HSA-6781823)
  Transcription-Coupled Nucleotide Excision Repair (TC-NER) (R-HSA-6781827)
  Dual incision in TC-NER (R-HSA-6782135)
  Gap-filling DNA repair synthesis and ligation in TC-NER (R-HSA-6782210)
  TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest (R-HSA-6804114)
  Regulation of TP53 Activity through Acetylation (R-HSA-6804758)
  Regulation of TP53 Activity through Methylation (R-HSA-6804760)
  PI5P Regulates TP53 Acetylation (R-HSA-6811555)
  Activation of the TFAP2 (AP-2) family of transcription factors (R-HSA-8866907)
  RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function (R-HSA-8936459)
  RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known (R-HSA-8939243)
  RUNX3 regulates NOTCH signaling (R-HSA-8941856)
  Regulation of RUNX3 expression and activity (R-HSA-8941858)
  RUNX3 regulates p14-ARF (R-HSA-8951936)
  NOTCH3 Intracellular Domain Regulates Transcription (R-HSA-9013508)
  NOTCH4 Intracellular Domain Regulates Transcription (R-HSA-9013695)
  Estrogen-dependent gene expression (R-HSA-9018519)
  NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux (R-HSA-9029569)
  NGF-stimulated transcription (R-HSA-9031628)
  TRAF3-dependent IRF activation pathway (R-HSA-918233)
  TRAF6 mediated IRF7 activation (R-HSA-933541)
  FOXO-mediated transcription of cell death genes (R-HSA-9614657)
  Transcriptional regulation of granulopoiesis (R-HSA-9616222)
  Regulation of FOXO transcriptional activity by acetylation (R-HSA-9617629)
  STAT3 nuclear events downstream of ALK signaling (R-HSA-9701898)
  Heme signaling (R-HSA-9707616)
  SARS-CoV-1 targets host intracellular signalling and regulatory pathways (R-HSA-9735871)
  Nuclear events mediated by NFE2L2 (R-HSA-9759194)
  Formation of paraxial mesoderm (R-HSA-9793380)
  NFE2L2 regulating inflammation associated genes (R-HSA-9818026)
  NFE2L2 regulating anti-oxidant/detoxification enzymes (R-HSA-9818027)
  NFE2L2 regulates pentose phosphate pathway genes (R-HSA-9818028)
  NFE2L2 regulating tumorigenic genes (R-HSA-9818030)
  NFE2L2 regulating MDR associated enzymes (R-HSA-9818032)
  NFE2L2 regulating ER-stress associated genes (R-HSA-9818035)
  Regulation of NFE2L2 gene expression (R-HSA-9818749)
  Zygotic genome activation (ZGA) (R-HSA-9819196)
  Regulation of gene expression by Hypoxia-inducible Factor (R-HSA-1234158)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Rubinstein-Taybi syndrome	DISVF1HM	Definitive	Autosomal dominant	[1]
Rubinstein-Taybi syndrome due to EP300 haploinsufficiency	DIS8TFX5	Definitive	Autosomal dominant	[2]

5 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 Histone acetyltransferase p300 (EP300).	[3]
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of Histone acetyltransferase p300 (EP300).	[12]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Histone acetyltransferase p300 (EP300).	[23]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Histone acetyltransferase p300 (EP300).	[25]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Histone acetyltransferase p300 (EP300).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Histone acetyltransferase p300 (EP300).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Histone acetyltransferase p300 (EP300).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Histone acetyltransferase p300 (EP300).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Histone acetyltransferase p300 (EP300).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Histone acetyltransferase p300 (EP300).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Histone acetyltransferase p300 (EP300).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Histone acetyltransferase p300 (EP300).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Histone acetyltransferase p300 (EP300).	[11]
Marinol	DM70IK5	Approved	Marinol increases the expression of Histone acetyltransferase p300 (EP300).	[13]
Menadione	DMSJDTY	Approved	Menadione decreases the expression of Histone acetyltransferase p300 (EP300).	[14]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Histone acetyltransferase p300 (EP300).	[15]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Histone acetyltransferase p300 (EP300).	[16]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Histone acetyltransferase p300 (EP300).	[17]
Enzalutamide	DMGL19D	Approved	Enzalutamide affects the expression of Histone acetyltransferase p300 (EP300).	[18]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Histone acetyltransferase p300 (EP300).	[19]
Berberine	DMC5Q8X	Phase 4	Berberine increases the expression of Histone acetyltransferase p300 (EP300).	[20]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Histone acetyltransferase p300 (EP300).	[21]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Histone acetyltransferase p300 (EP300).	[22]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin decreases the expression of Histone acetyltransferase p300 (EP300).	[5]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Histone acetyltransferase p300 (EP300).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Histone acetyltransferase p300 (EP300).	[24]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Histone acetyltransferase p300 (EP300).	[26]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Histone acetyltransferase p300 (EP300).	[27]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Histone acetyltransferase p300 (EP300).	[28]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Histone acetyltransferase p300 (EP300).	[29]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Histone acetyltransferase p300 (EP300).	[30]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Histone acetyltransferase p300 (EP300).	[31]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Histone acetyltransferase p300 (EP300).	[32]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Histone acetyltransferase p300 (EP300).	[33]
Okadaic acid	DM47CO1	Investigative	Okadaic acid decreases the expression of Histone acetyltransferase p300 (EP300).	[34]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID increases the expression of Histone acetyltransferase p300 (EP300).	[35]
aconitine	DMFOZ60	Investigative	aconitine affects the expression of Histone acetyltransferase p300 (EP300).	[37]
PGJ2	DMR2LTC	Investigative	PGJ2 decreases the activity of Histone acetyltransferase p300 (EP300).	[38]
Delta12-PGJ2	DMB6ADI	Investigative	Delta12-PGJ2 decreases the activity of Histone acetyltransferase p300 (EP300).	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
15-deoxy-Delta(12, 14)-prostaglandin J(2)	DM8VUX3	Investigative	15-deoxy-Delta(12, 14)-prostaglandin J(2) decreases the localization of Histone acetyltransferase p300 (EP300).	[36]

References

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• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] Nuclear and Mitochondrial DNA Methylation Patterns Induced by Valproic Acid in Human Hepatocytes. Chem Res Toxicol. 2017 Oct 16;30(10):1847-1854. doi: 10.1021/acs.chemrestox.7b00171. Epub 2017 Sep 13.
• [4] Histone Acetyltransferase p300/CREB-binding Protein-associated Factor (PCAF) Is Required for All-trans-retinoic Acid-induced Granulocytic Differentiation in Leukemia Cells. J Biol Chem. 2017 Feb 17;292(7):2815-2829. doi: 10.1074/jbc.M116.745398. Epub 2017 Jan 4.
• [5] Coordinate alterations in the expression of BRCA1, BRCA2, p300, and Rad51 in response to genotoxic and other stresses in human prostate cancer cells. Prostate. 1999 Jun 15;40(1):37-49. doi: 10.1002/(sici)1097-0045(19990615)40:1<37::aid-pros5>3.0.co;2-p.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Cisplatin and doxorubicin repress Vascular Endothelial Growth Factor expression and differentially down-regulate Hypoxia-inducible Factor I activity in human ovarian cancer cells. Biochem Pharmacol. 2007 Jul 15;74(2):191-201. doi: 10.1016/j.bcp.2007.04.003. Epub 2007 Apr 6.
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• [9] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [10] Suppression of transforming growth factor beta/smad signaling in keloid-derived fibroblasts by quercetin: implications for the treatment of excessive scars. J Trauma. 2004 Nov;57(5):1032-7. doi: 10.1097/01.ta.0000114087.46566.eb.
• [11] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [12] p300 expression repression by hypermethylation associated with tumour invasion and metastasis in oesophageal squamous cell carcinoma. J Clin Pathol. 2007 Nov;60(11):1249-53. doi: 10.1136/jcp.2006.044099.
• [13] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [14] Vitamin K3 (menadione) suppresses epithelial-mesenchymal-transition and Wnt signaling pathway in human colorectal cancer cells. Chem Biol Interact. 2019 Aug 25;309:108725. doi: 10.1016/j.cbi.2019.108725. Epub 2019 Jun 22.
• [15] Growth inhibition of ovarian tumor-initiating cells by niclosamide. Mol Cancer Ther. 2012 Aug;11(8):1703-12.
• [16] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [17] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [18] NOTCH signaling is activated in and contributes to resistance in enzalutamide-resistant prostate cancer cells. J Biol Chem. 2019 May 24;294(21):8543-8554. doi: 10.1074/jbc.RA118.006983. Epub 2019 Apr 2.
• [19] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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