Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT18UX57)

DOT Name	Histone H2AX (H2AX)
Synonyms	H2a/x; Histone H2A.X
Gene Name	H2AX
Related Disease	Adult glioblastoma ( ) Adult lymphoma ( ) Ataxia-telangiectasia ( ) Bone osteosarcoma ( ) Breast cancer ( ) Breast carcinoma ( ) Carcinoma ( ) Colon cancer ( ) Colon carcinoma ( ) Colorectal carcinoma ( ) Fanconi anemia complementation group A ( ) Fanconi's anemia ( ) Glioblastoma multiforme ( ) Hepatocellular carcinoma ( ) High blood pressure ( ) Huntington disease ( ) Hutchinson-Gilford progeria syndrome ( ) leukaemia ( ) Leukemia ( ) Liver and intrahepatic bile duct neoplasm ( ) Multiple sclerosis ( ) Neoplasm ( ) Non-hodgkin lymphoma ( ) Non-small-cell lung cancer ( ) Obesity ( ) Osteosarcoma ( ) Ovarian cancer ( ) Pediatric lymphoma ( ) Schizophrenia ( ) Squamous cell carcinoma ( ) Ulcerative colitis ( ) Breast neoplasm ( ) Glioma ( ) Lung cancer ( ) Melanoma ( ) Prostate cancer ( ) Prostate carcinoma ( ) Triple negative breast cancer ( ) Chromosomal disorder ( ) Endometrial carcinoma ( ) Lung carcinoma ( ) Nasopharyngeal carcinoma ( ) Retinoblastoma ( ) Status epilepticus seizure ( )
UniProt ID	H2AX_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1YDP; 2AZM; 2D31; 2DYP; 3SHV; 3SQD; 3SZM; 3U3Z; 6K1I; 6K1J; 6K1K; 6ZWK; 7YQK
Pfam ID	PF00125 ; PF16211
Sequence	MSGRGKTGGKARAKAKSRSSRAGLQFPVGRVHRLLRKGHYAERVGAGAPVYLAAVLEYLT AEILELAGNAARDNKKTRIIPRHLQLAIRNDEELNKLLGGVTIAQGGVLPNIQAVLLPKK TSATVGPKAPSGGKKATQASQEY
Function	Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. 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. Required for checkpoint-mediated arrest of cell cycle progression in response to low doses of ionizing radiation and for efficient repair of DNA double strand breaks (DSBs) specifically when modified by C-terminal phosphorylation.
KEGG Pathway	ATP-dependent chromatin remodeling (hsa03082 ) Necroptosis (hsa04217 ) Neutrophil extracellular trap formation (hsa04613 ) Alcoholism (hsa05034 ) 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 ) 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 ) 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 ) 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

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[2]
Ataxia-telangiectasia	DISP3EVR	Strong	Altered Expression	[3]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[5]
Carcinoma	DISH9F1N	Strong	Biomarker	[6]
Colon cancer	DISVC52G	Strong	Genetic Variation	[7]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[8]
Fanconi anemia complementation group A	DIS8PZLI	Strong	Biomarker	[9]
Fanconi's anemia	DISGW6Q8	Strong	Biomarker	[9]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[10]
High blood pressure	DISY2OHH	Strong	Therapeutic	[11]
Huntington disease	DISQPLA4	Strong	Biomarker	[12]
Hutchinson-Gilford progeria syndrome	DISY55BU	Strong	Biomarker	[13]
leukaemia	DISS7D1V	Strong	Posttranslational Modification	[14]
Leukemia	DISNAKFL	Strong	Posttranslational Modification	[14]
Liver and intrahepatic bile duct neoplasm	DISRQ76N	Strong	Therapeutic	[15]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[16]
Neoplasm	DISZKGEW	Strong	Biomarker	[17]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Genetic Variation	[18]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[19]
Obesity	DIS47Y1K	Strong	Biomarker	[20]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[4]
Ovarian cancer	DISZJHAP	Strong	Genetic Variation	[21]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[2]
Schizophrenia	DISSRV2N	Strong	Biomarker	[22]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[23]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[24]
Breast neoplasm	DISNGJLM	moderate	Biomarker	[25]
Glioma	DIS5RPEH	moderate	Altered Expression	[26]
Lung cancer	DISCM4YA	moderate	Genetic Variation	[27]
Melanoma	DIS1RRCY	moderate	Altered Expression	[28]
Prostate cancer	DISF190Y	moderate	Biomarker	[29]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[29]
Triple negative breast cancer	DISAMG6N	moderate	Posttranslational Modification	[30]
Chromosomal disorder	DISM5BB5	Limited	Biomarker	[31]
Endometrial carcinoma	DISXR5CY	Limited	Biomarker	[32]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[27]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[33]
Retinoblastoma	DISVPNPB	Limited	Biomarker	[34]
Status epilepticus seizure	DISY3BIC	Limited	Biomarker	[35]
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⏷ Show the Full List of 44 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Resveratrol	DM3RWXL	Phase 3	Histone H2AX (H2AX) increases the response to substance of Resveratrol.	[120]
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70 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Histone H2AX (H2AX).	[36]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Histone H2AX (H2AX).	[37]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Histone H2AX (H2AX).	[38]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Histone H2AX (H2AX).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Histone H2AX (H2AX).	[40]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Histone H2AX (H2AX).	[41]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Histone H2AX (H2AX).	[42]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Histone H2AX (H2AX).	[43]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Histone H2AX (H2AX).	[44]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Histone H2AX (H2AX).	[47]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Histone H2AX (H2AX).	[48]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Histone H2AX (H2AX).	[49]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the activity of Histone H2AX (H2AX).	[50]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Histone H2AX (H2AX).	[49]
Carbamazepine	DMZOLBI	Approved	Carbamazepine increases the expression of Histone H2AX (H2AX).	[51]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Histone H2AX (H2AX).	[53]
Marinol	DM70IK5	Approved	Marinol increases the expression of Histone H2AX (H2AX).	[54]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Histone H2AX (H2AX).	[55]
Selenium	DM25CGV	Approved	Selenium increases the expression of Histone H2AX (H2AX).	[56]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Histone H2AX (H2AX).	[57]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Histone H2AX (H2AX).	[59]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Histone H2AX (H2AX).	[54]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Histone H2AX (H2AX).	[60]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Histone H2AX (H2AX).	[62]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Histone H2AX (H2AX).	[63]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Histone H2AX (H2AX).	[64]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Histone H2AX (H2AX).	[65]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Histone H2AX (H2AX).	[67]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Histone H2AX (H2AX).	[68]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Histone H2AX (H2AX).	[69]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Histone H2AX (H2AX).	[68]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the expression of Histone H2AX (H2AX).	[70]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Histone H2AX (H2AX).	[71]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Histone H2AX (H2AX).	[72]
Mitomycin	DMH0ZJE	Approved	Mitomycin increases the expression of Histone H2AX (H2AX).	[70]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Histone H2AX (H2AX).	[53]
Topotecan	DMP6G8T	Approved	Topotecan increases the expression of Histone H2AX (H2AX).	[74]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Histone H2AX (H2AX).	[75]
Mitoxantrone	DMM39BF	Approved	Mitoxantrone increases the expression of Histone H2AX (H2AX).	[76]
Daunorubicin	DMQUSBT	Approved	Daunorubicin increases the expression of Histone H2AX (H2AX).	[79]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea increases the expression of Histone H2AX (H2AX).	[84]
Imatinib	DM7RJXL	Approved	Imatinib increases the expression of Histone H2AX (H2AX).	[85]
Dactinomycin	DM2YGNW	Approved	Dactinomycin increases the expression of Histone H2AX (H2AX).	[86]
Docetaxel	DMDI269	Approved	Docetaxel increases the expression of Histone H2AX (H2AX).	[19]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol decreases the expression of Histone H2AX (H2AX).	[67]
2-deoxyglucose	DMIAHVU	Approved	2-deoxyglucose decreases the expression of Histone H2AX (H2AX).	[67]
Dihydroxyacetone	DMM1LG2	Approved	Dihydroxyacetone increases the expression of Histone H2AX (H2AX).	[89]
Bleomycin	DMNER5S	Approved	Bleomycin increases the expression of Histone H2AX (H2AX).	[84]
Lapatinib	DM3BH1Y	Approved	Lapatinib increases the expression of Histone H2AX (H2AX).	[92]
Trovafloxacin	DM6AN32	Approved	Trovafloxacin increases the expression of Histone H2AX (H2AX).	[93]
Fludarabine	DMVRLT7	Approved	Fludarabine increases the expression of Histone H2AX (H2AX).	[98]
Olaparib	DM8QB1D	Approved	Olaparib increases the expression of Histone H2AX (H2AX).	[100]
Fotemustine	DMV62ED	Approved	Fotemustine increases the expression of Histone H2AX (H2AX).	[103]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of Histone H2AX (H2AX).	[104]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin increases the expression of Histone H2AX (H2AX).	[106]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Histone H2AX (H2AX).	[107]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of Histone H2AX (H2AX).	[108]
Triptolide	DMCMDVR	Phase 3	Triptolide increases the expression of Histone H2AX (H2AX).	[109]
Remdesivir	DMBFZ6L	Phase 3 Trial	Remdesivir increases the expression of Histone H2AX (H2AX).	[110]
NVP-LAQ824	DM8JWNA	Phase 3	NVP-LAQ824 increases the expression of Histone H2AX (H2AX).	[98]
Selinexor	DMBD4K3	Phase 3	Selinexor increases the expression of Histone H2AX (H2AX).	[111]
MK-4827	DMLYGH4	Phase 3	MK-4827 increases the expression of Histone H2AX (H2AX).	[112]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Histone H2AX (H2AX).	[43]
APR-246	DMNFADH	Phase 2	APR-246 increases the expression of Histone H2AX (H2AX).	[115]
Disulfiram	DMCL2OK	Phase 2 Trial	Disulfiram increases the expression of Histone H2AX (H2AX).	[116]
Flavopiridol	DMKSUOI	Phase 2	Flavopiridol affects the expression of Histone H2AX (H2AX).	[117]
PF-04991532	DM94NBE	Phase 2	PF-04991532 increases the expression of Histone H2AX (H2AX).	[108]
Itarnafloxin	DMCY9PO	Phase 2	Itarnafloxin increases the expression of Histone H2AX (H2AX).	[118]
Triapine	DM7XZY5	Phase 2	Triapine increases the expression of Histone H2AX (H2AX).	[84]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 increases the expression of Histone H2AX (H2AX).	[119]
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⏷ Show the Full List of 70 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of Histone H2AX (H2AX).	[45]
Temozolomide	DMKECZD	Approved	Temozolomide increases the phosphorylation of Histone H2AX (H2AX).	[46]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the phosphorylation of Histone H2AX (H2AX).	[52]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the phosphorylation of Histone H2AX (H2AX).	[58]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the phosphorylation of Histone H2AX (H2AX).	[61]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the phosphorylation of Histone H2AX (H2AX).	[66]
Simvastatin	DM30SGU	Approved	Simvastatin increases the phosphorylation of Histone H2AX (H2AX).	[73]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the phosphorylation of Histone H2AX (H2AX).	[61]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the phosphorylation of Histone H2AX (H2AX).	[77]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the phosphorylation of Histone H2AX (H2AX).	[80]
Acocantherin	DM7JT24	Approved	Acocantherin increases the phosphorylation of Histone H2AX (H2AX).	[81]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the phosphorylation of Histone H2AX (H2AX).	[82]
Lindane	DMB8CNL	Approved	Lindane increases the phosphorylation of Histone H2AX (H2AX).	[83]
Etretinate	DM2CZFA	Approved	Etretinate increases the phosphorylation of Histone H2AX (H2AX).	[87]
Artesunate	DMR27C8	Approved	Artesunate increases the phosphorylation of Histone H2AX (H2AX).	[88]
Crizotinib	DM4F29C	Approved	Crizotinib increases the phosphorylation of Histone H2AX (H2AX).	[90]
Romidepsin	DMT5GNL	Approved	Romidepsin increases the phosphorylation of Histone H2AX (H2AX).	[91]
Chlorambucil	DMRKE63	Approved	Chlorambucil increases the phosphorylation of Histone H2AX (H2AX).	[94]
Busulfan	DMXYJ9C	Approved	Busulfan increases the phosphorylation of Histone H2AX (H2AX).	[95]
Amsacrine	DMZKYIV	Approved	Amsacrine increases the phosphorylation of Histone H2AX (H2AX).	[96]
AC220	DM8Y4JS	Approved	AC220 increases the phosphorylation of Histone H2AX (H2AX).	[91]
Dronedarone	DMA8FS5	Approved	Dronedarone increases the phosphorylation of Histone H2AX (H2AX).	[99]
Pyrimethamine	DM5X7VY	Approved	Pyrimethamine increases the phosphorylation of Histone H2AX (H2AX).	[101]
Norethindrone	DMTY169	Approved	Norethindrone increases the phosphorylation of Histone H2AX (H2AX).	[102]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the phosphorylation of Histone H2AX (H2AX).	[91]
Curcumin	DMQPH29	Phase 3	Curcumin increases the phosphorylation of Histone H2AX (H2AX).	[105]
Thymoquinone	DMVDTR2	Phase 2/3	Thymoquinone increases the phosphorylation of Histone H2AX (H2AX).	[114]
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⏷ Show the Full List of 27 Drug(s)

3 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 Histone H2AX (H2AX).	[78]
Pentamidine	DMHZJCG	Approved	Pentamidine affects the localization of Histone H2AX (H2AX).	[97]
Phenol	DM1QSM3	Phase 2/3	Phenol affects the localization of Histone H2AX (H2AX).	[113]
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