Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB71W46)

• DOT Name: Histone H4 (H4C1)
• Gene Name: H4C1
• Related Disease:
  Breast carcinoma
  Acute lymphocytic leukaemia
  Acute myelogenous leukaemia
  Adult lymphoma
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Autoimmune disease
  B-cell neoplasm
  Bone osteosarcoma
  Breast cancer
  Carcinoma
  Castration-resistant prostate carcinoma
  Clear cell renal carcinoma
  Endometrial cancer
  Endometrial carcinoma
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Gastric cancer
  Glioma
  Hepatocellular carcinoma
  Intellectual disability
  leukaemia
  Leukemia
  Lung cancer
  Lung carcinoma
  Lymphoma
  Neoplasm
  Osteosarcoma
  Ovarian cancer
  Ovarian neoplasm
  Pediatric lymphoma
  Renal cell carcinoma
  Rheumatoid arthritis
  Schizophrenia
  Stomach cancer
  Systemic lupus erythematosus
  Tessadori-Van Haaften neurodevelopmental syndrome 3
  Tuberculosis
  Adult glioblastoma
  Breast neoplasm
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Glioblastoma multiforme
  Pancreatic cancer
  Tessadori-van Haaften neurodevelopmental syndrome 1
  Advanced cancer
  Asthma
  Neuroblastoma
  Squamous cell carcinoma
  Tessadori-van Haaften neurodevelopmental syndrome 2
  Tessadori-Van Haaften neurodevelopmental syndrome 4
• UniProt ID: H4_HUMAN
• PDB ID: 1ZKK ; 2BQZ ; 2CV5 ; 2IG0 ; 2KWN ; 2KWO ; 2LVM ; 2QQS ; 2RJE ; 2RNY ; 2RS9 ; 3A6N ; 3AFA ; 3AN2 ; 3AV1 ; 3AV2 ; 3AYW ; 3AZE ; 3AZF ; 3AZG ; 3AZH ; 3AZI ; 3AZJ ; 3AZK ; 3AZL ; 3AZM ; 3AZN ; 3CFS ; 3CFV ; 3F9W ; 3F9X ; 3F9Y ; 3F9Z ; 3IJ1 ; 3JPX ; 3NQJ ; 3NQU ; 3O36 ; 3QBY ; 3QZS ; 3QZT ; 3QZV ; 3R45 ; 3UVW ; 3UVX ; 3UVY ; 3UW9 ; 3W96 ; 3W97 ; 3W98 ; 3W99 ; 3WA9 ; 3WAA ; 3WKJ ; 3WTP ; 3X1S ; 3X1T ; 3X1U ; 3X1V ; 4GQB ; 4H9N ; 4H9O ; 4H9P ; 4H9Q ; 4H9R ; 4H9S ; 4HGA ; 4M38 ; 4N3W ; 4N4F ; 4QUT ; 4QUU ; 4QYD ; 4U9W ; 4YM5 ; 4YM6 ; 4YY6 ; 4YYD ; 4YYG ; 4YYH ; 4YYI ; 4YYJ ; 4YYK ; 4YYM ; 4YYN ; 4Z2M ; 4Z5T ; 5AV5 ; 5AV6 ; 5AV8 ; 5AV9 ; 5AVB ; 5AVC ; 5AY8 ; 5B0Y ; 5B0Z ; 5B24 ; 5B2I ; 5B2J ; 5B31 ; 5B32 ; 5B33 ; 5B40 ; 5BNV ; 5BNX ; 5BO0 ; 5C3I ; 5CPI ; 5CPJ ; 5CPK ; 5FA5 ; 5FFW ; 5FWE ; 5GSE ; 5GSU ; 5GT0 ; 5GT3 ; 5GTC ; 5GXQ ; 5JA4 ; 5JRG ; 5KDM ; 5TEG ; 5X7X ; 5XF3 ; 5XF4 ; 5XF5 ; 5Y0C ; 5Y0D ; 5YE3 ; 5YE4 ; 5Z23 ; 5Z30 ; 5ZBX ; 5ZGC ; 6A5L ; 6A5O ; 6A5P ; 6A5R ; 6A5T ; 6A5U ; 6ACP ; 6BUZ ; 6C0W ; 6E0C ; 6E0P ; 6FML ; 6HKT ; 6HTS ; 6INQ ; 6IR9 ; 6J4W ; 6J4X ; 6J4Y ; 6J4Z ; 6J50 ; 6J51 ; 6JOU ; 6JR0 ; 6JR1 ; 6K1I ; 6K1J ; 6K1K ; 6KE9 ; 6KVD ; 6KXV ; 6L49 ; 6L4A ; 6L9H ; 6L9Z ; 6LA2 ; 6LA8 ; 6LA9 ; 6LAB ; 6LE9 ; 6LER ; 6M3V ; 6M44 ; 6M4D ; 6M4G ; 6M4H ; 6MLC ; 6MUO ; 6MUP ; 6O1D ; 6R0C ; 6R8Y ; 6R8Z ; 6R90 ; 6R91 ; 6R92 ; 6R93 ; 6R94 ; 6RNY ; 6RXS ; 6SE0 ; 6SE6 ; 6SEE ; 6SEF ; 6SEG ; 6T79 ; 6T7A ; 6T7B ; 6T7C ; 6T7D ; 6T90 ; 6T93 ; 6UPK ; 6UPL ; 6USJ ; 6V2K ; 6V92 ; 6VO5 ; 6X59 ; 6X5A ; 6XJD ; 6Y5D ; 6YOV ; 7A08 ; 7BWD ; 7BXT ; 7BY0 ; 7C0M ; 7CCQ ; 7CCR ; 7CIZ ; 7CJ0 ; 7COW ; 7D1Z ; 7D20 ; 7DBP ; 7E8D ; 7EIC ; 7EID ; 7JO9 ; 7JOA ; 7JZV ; 7K5X ; 7K5Y ; 7K60 ; 7K61 ; 7K63 ; 7LMK ; 7LMM ; 7LYA ; 7LYB ; 7LYC ; 7M98 ; 7NL0 ; 7PET ; 7PEU ; 7PEV ; 7PEW ; 7PEX ; 7PEY ; 7PEZ ; 7PF0 ; 7PF2 ; 7PF3 ; 7PF4 ; 7PF5 ; 7PF6 ; 7PFA ; 7PFC ; 7PFD ; 7PFE ; 7PFF ; 7PFT ; 7PFU ; 7PFV ; 7PFW ; 7PFX ; 7PII ; 7R5R ; 7SCY ; 7SCZ ; 7TAN ; 7U0G ; 7U0I ; 7U0J ; 7U46 ; 7U47 ; 7U4D ; 7U50 ; 7U51 ; 7U52 ; 7U53 ; 7UV9 ; 7V1M ; 7V6Q ; 7V90 ; 7V96 ; 7V9C ; 7V9J ; 7V9K ; 7V9S ; 7VA4 ; 7VCQ ; 7VZ4 ; 7W9V ; 7WBV ; 7WBW ; 7WBX ; 7X57 ; 7X58 ; 7XCR ; 7XCT ; 7XD0 ; 7XD1 ; 7XSE ; 7XSX ; 7XSZ ; 7XT7 ; 7XTD ; 7XTI ; 7XVL ; 7XVM ; 7XX5 ; 7XX6 ; 7XX7 ; 7XZX ; 7XZY ; 7XZZ ; 7Y00 ; 7Y5U ; 7Y5V ; 7Y5W ; 7Y60 ; 7Y61 ; 7Y7I ; 7Y8R ; 7YOZ ; 7YQK ; 7YRD ; 7YWX ; 7YYH ; 7ZI4 ; 8AAG ; 8ATF ; 8AV6 ; 8B5A ; 8B5B ; 8B5C ; 8DK5 ; 8EVG ; 8EVH ; 8EVI ; 8EVJ ; 8GUI ; 8GUJ ; 8GUK ; 8H0V ; 8H0W ; 8H1T ; 8HAG ; 8HAH ; 8HAI ; 8HAJ ; 8HAK ; 8HAL ; 8HAM ; 8HAN ; 8HE5 ; 8HLW ; 8IEG ; 8IEJ ; 8IQF ; 8IQG ; 8J6S ; 8J6T ; 8JH2 ; 8JH3 ; 8JH4 ; 8JHF ; 8JHG ; 8JL9 ; 8JLA ; 8JLB ; 8JLD ; 8KB5 ; 8OFF ; 8OO7 ; 8OOA ; 8OOP ; 8OOS ; 8OSJ ; 8OSK ; 8OSL ; 8OTS ; 8OTT ; 8OX0 ; 8OX1 ; 8SB6 ; 8SPS ; 8SPU ; 8SYP
• Pfam ID: PF15511
• Sequence:
  MSGRGKGGKGLGKGGAKRHRKVLRDNIQGITKPAIRRLARRGGVKRISGLIYEETRGVLK
  VFLENVIRDAVTYTEHAKRKTVTAMDVVYALKRQGRTLYGFGG
• Function: Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
• KEGG Pathway:
  Neutrophil extracellular trap formation (hsa04613)
  Alcoholism (hsa05034)
  Viral carcinogenesis (hsa05203)
  Systemic lupus erythematosus (hsa05322)
• Reactome Pathway:
  Cleavage of the damaged pyrimidine (R-HSA-110329)
  Recognition and association of DNA glycosylase with site containing an affected purine (R-HSA-110330)
  Cleavage of the damaged purine (R-HSA-110331)
  Meiotic synapsis (R-HSA-1221632)
  Packaging Of Telomere Ends (R-HSA-171306)
  Pre-NOTCH Transcription and Translation (R-HSA-1912408)
  Formation of the beta-catenin (R-HSA-201722)
  PRC2 methylates histones and DNA (R-HSA-212300)
  Condensation of Prophase Chromosomes (R-HSA-2299718)
  Oxidative Stress Induced Senescence (R-HSA-2559580)
  Senescence-Associated Secretory Phenotype (SASP) (R-HSA-2559582)
  DNA Damage/Telomere Stress Induced Senescence (R-HSA-2559586)
  HDACs deacetylate histones (R-HSA-3214815)
  PKMTs methylate histone lysines (R-HSA-3214841)
  HDMs demethylate histones (R-HSA-3214842)
  HATs acetylate histones (R-HSA-3214847)
  RMTs methylate histone arginines (R-HSA-3214858)
  SIRT1 negatively regulates rRNA expression (R-HSA-427359)
  ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression (R-HSA-427389)
  NoRC negatively regulates rRNA expression (R-HSA-427413)
  SUMOylation of chromatin organization proteins (R-HSA-4551638)
  B-WICH complex positively regulates rRNA expression (R-HSA-5250924)
  DNA methylation (R-HSA-5334118)
  Transcriptional regulation by small RNAs (R-HSA-5578749)
  Activation of anterior HOX genes in hindbrain development during early embryogenesis (R-HSA-5617472)
  Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 (R-HSA-5625886)
  Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks (R-HSA-5693565)
  Nonhomologous End-Joining (NHEJ) (R-HSA-5693571)
  Processing of DNA double-strand break ends (R-HSA-5693607)
  Deposition of new CENPA-containing nucleosomes at the centromere (R-HSA-606279)
  Assembly of the ORC complex at the origin of replication (R-HSA-68616)
  G2/M DNA damage checkpoint (R-HSA-69473)
  RNA Polymerase I Promoter Opening (R-HSA-73728)
  RNA Polymerase I Promoter Escape (R-HSA-73772)
  RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function (R-HSA-8936459)
  RUNX1 regulates transcription of genes involved in differentiation of HSCs (R-HSA-8939236)
  Estrogen-dependent gene expression (R-HSA-9018519)
  Meiotic recombination (R-HSA-912446)
  HCMV Early Events (R-HSA-9609690)
  HCMV Late Events (R-HSA-9610379)
  Transcriptional regulation of granulopoiesis (R-HSA-9616222)
  Inhibition of DNA recombination at telomere (R-HSA-9670095)
  Defective pyroptosis (R-HSA-9710421)
  Amyloid fiber formation (R-HSA-977225)
  Chromatin modifications during the maternal to zygotic transition (MZT) (R-HSA-9821002)
  Replacement of protamines by nucleosomes in the male pronucleus (R-HSA-9821993)
  Recognition and association of DNA glycosylase with site containing an affected pyrimidine (R-HSA-110328)

Molecular Interaction Atlas (MIA) of This DOT

53 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast carcinoma	DIS2UE88	Definitive	Genetic Variation	[1]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[3]
Adult lymphoma	DISK8IZR	Strong	Genetic Variation	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[6]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[6]
Autoimmune disease	DISORMTM	Strong	Biomarker	[7]
B-cell neoplasm	DISVY326	Strong	Genetic Variation	[8]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[9]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[1]
Carcinoma	DISH9F1N	Strong	Biomarker	[10]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Posttranslational Modification	[11]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[12]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[13]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[13]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[14]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[15]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[16]
Glioma	DIS5RPEH	Strong	Biomarker	[17]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[18]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[19]
leukaemia	DISS7D1V	Strong	Altered Expression	[20]
Leukemia	DISNAKFL	Strong	Altered Expression	[20]
Lung cancer	DISCM4YA	Strong	Biomarker	[21]
Lung carcinoma	DISTR26C	Strong	Biomarker	[21]
Lymphoma	DISN6V4S	Strong	Genetic Variation	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[22]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[9]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[14]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[14]
Pediatric lymphoma	DIS51BK2	Strong	Genetic Variation	[4]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[12]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[23]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[24]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[16]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[25]
Tessadori-Van Haaften neurodevelopmental syndrome 3	DISGUZY7	Strong	Autosomal dominant	[26]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[27]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[28]
Breast neoplasm	DISNGJLM	moderate	Posttranslational Modification	[29]
Colon cancer	DISVC52G	moderate	Biomarker	[22]
Colon carcinoma	DISJYKUO	moderate	Biomarker	[22]
Colorectal carcinoma	DIS5PYL0	moderate	Altered Expression	[30]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[28]
Pancreatic cancer	DISJC981	moderate	Biomarker	[31]
Tessadori-van Haaften neurodevelopmental syndrome 1	DISGLNNY	Moderate	Autosomal dominant	[26]
Advanced cancer	DISAT1Z9	Limited	Posttranslational Modification	[32]
Asthma	DISW9QNS	Limited	Biomarker	[33]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[34]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[35]
Tessadori-van Haaften neurodevelopmental syndrome 2	DISLN90E	Limited	Autosomal dominant	[26]
Tessadori-Van Haaften neurodevelopmental syndrome 4	DISDL3G7	Limited	Autosomal dominant	[26]

11 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 H4 (H4C1).	[36]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Histone H4 (H4C1).	[45]
Panobinostat	DM58WKG	Approved	Panobinostat increases the acetylation of Histone H4 (H4C1).	[60]
MGCD-0103	DM726HX	Phase 2	MGCD-0103 increases the acetylation of Histone H4 (H4C1).	[60]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Histone H4 (H4C1).	[89]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Histone H4 (H4C1).	[91]
SK-7041	DM7DNOG	Preclinical	SK-7041 increases the acetylation of Histone H4 (H4C1).	[93]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Histone H4 (H4C1).	[94]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the acetylation of Histone H4 (H4C1).	[93]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the acetylation of Histone H4 (H4C1).	[100]
RGFP966	DME9T0A	Investigative	RGFP966 increases the acetylation of Histone H4 (H4C1).	[104]

64 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 Histone H4 (H4C1).	[37]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Histone H4 (H4C1).	[38]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Histone H4 (H4C1).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Histone H4 (H4C1).	[40]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Histone H4 (H4C1).	[41]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Histone H4 (H4C1).	[42]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Histone H4 (H4C1).	[43]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Histone H4 (H4C1).	[44]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Histone H4 (H4C1).	[46]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Histone H4 (H4C1).	[47]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Histone H4 (H4C1).	[48]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Histone H4 (H4C1).	[49]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Histone H4 (H4C1).	[50]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Histone H4 (H4C1).	[51]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Histone H4 (H4C1).	[52]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Histone H4 (H4C1).	[53]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Histone H4 (H4C1).	[54]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Histone H4 (H4C1).	[55]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Histone H4 (H4C1).	[56]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Histone H4 (H4C1).	[57]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Histone H4 (H4C1).	[58]
Menadione	DMSJDTY	Approved	Menadione decreases the expression of Histone H4 (H4C1).	[49]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Histone H4 (H4C1).	[59]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Histone H4 (H4C1).	[61]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Histone H4 (H4C1).	[62]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Histone H4 (H4C1).	[63]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Histone H4 (H4C1).	[64]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Histone H4 (H4C1).	[65]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Histone H4 (H4C1).	[66]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Histone H4 (H4C1).	[67]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Histone H4 (H4C1).	[68]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Histone H4 (H4C1).	[69]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Histone H4 (H4C1).	[70]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Histone H4 (H4C1).	[59]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Histone H4 (H4C1).	[71]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Histone H4 (H4C1).	[72]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Histone H4 (H4C1).	[73]
Aminoglutethimide	DMWFHMZ	Approved	Aminoglutethimide increases the expression of Histone H4 (H4C1).	[74]
Chlorambucil	DMRKE63	Approved	Chlorambucil decreases the expression of Histone H4 (H4C1).	[75]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Histone H4 (H4C1).	[76]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of Histone H4 (H4C1).	[77]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Histone H4 (H4C1).	[78]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Histone H4 (H4C1).	[79]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Histone H4 (H4C1).	[80]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Histone H4 (H4C1).	[81]
Nabiximols	DMHKJ5I	Phase 3	Nabiximols increases the expression of Histone H4 (H4C1).	[82]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Histone H4 (H4C1).	[83]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Histone H4 (H4C1).	[84]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Histone H4 (H4C1).	[57]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Histone H4 (H4C1).	[86]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Histone H4 (H4C1).	[87]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 affects the expression of Histone H4 (H4C1).	[88]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Histone H4 (H4C1).	[90]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Histone H4 (H4C1).	[80]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Histone H4 (H4C1).	[92]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Histone H4 (H4C1).	[62]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Histone H4 (H4C1).	[95]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Histone H4 (H4C1).	[96]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Histone H4 (H4C1).	[97]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Histone H4 (H4C1).	[98]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of Histone H4 (H4C1).	[99]
Okadaic acid	DM47CO1	Investigative	Okadaic acid decreases the expression of Histone H4 (H4C1).	[101]
Bilirubin	DMI0V4O	Investigative	Bilirubin increases the expression of Histone H4 (H4C1).	[102]
Paraoxon	DMN4ZKC	Investigative	Paraoxon decreases the expression of Histone H4 (H4C1).	[103]

2 Drug(s) Affected the Biochemical Pathways of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB increases the metabolism of Histone H4 (H4C1).	[85]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the metabolism of Histone H4 (H4C1).	[85]

References

• [1] A novel histone H4 variant H4G regulates rDNA transcription in breast cancer.Nucleic Acids Res. 2019 Sep 19;47(16):8399-8409. doi: 10.1093/nar/gkz547.
• [2] Preserved global histone H4 acetylation linked to ETV6-RUNX1 fusion and PAX5 deletions is associated with favorable outcome in pediatric B-cell progenitor acute lymphoblastic leukemia.Leuk Res. 2015 Dec;39(12):1455-61. doi: 10.1016/j.leukres.2015.10.006. Epub 2015 Oct 20.
• [3] MYST2 acetyltransferase expression and Histone H4 Lysine acetylation are suppressed in AML.Exp Hematol. 2015 Sep;43(9):794-802.e4. doi: 10.1016/j.exphem.2015.05.010. Epub 2015 Jun 11.
• [4] Epigenetic control via allosteric regulation of mammalian protein arginine methyltransferases.Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):10101-10106. doi: 10.1073/pnas.1706978114. Epub 2017 Sep 5.
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