Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0AVI4M)

• DOT Name: Histone H1.2 (H1-2)
• Synonyms: Histone H1c; Histone H1d; Histone H1s-1
• Gene Name: H1-2
• Related Disease:
  Acute myelogenous leukaemia
  Neoplasm
  Type-1/2 diabetes
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Diabetic retinopathy
  Gout
  Influenza
  Neuroblastoma
• UniProt ID: H12_HUMAN
• PDB ID: 8H0V; 8H0W
• Pfam ID: PF00538
• Sequence:
  MSETAPAAPAAAPPAEKAPVKKKAAKKAGGTPRKASGPPVSELITKAVAASKERSGVSLA
  ALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKAASGEAKPKV
  KKAGGTKPKKPVGAAKKPKKAAGGATPKKSAKKTPKKAKKPAAATVTKKVAKSPKKAKVA
  KPKKAAKSAAKAVKPKAAKPKVVKPKKAAPKKK
• Function: Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Acts also as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation.
• Reactome Pathway:
  Formation of Senescence-Associated Heterochromatin Foci (SAHF) (R-HSA-2559584)
  Apoptosis induced DNA fragmentation (R-HSA-140342)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Genetic Variation	[1]
Neoplasm	DISZKGEW	Definitive	Altered Expression	[2]
Type-1/2 diabetes	DISIUHAP	Definitive	Altered Expression	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Diabetic retinopathy	DISHGUJM	Strong	Altered Expression	[3]
Gout	DISHC0U7	Strong	Genetic Variation	[5]
Influenza	DIS3PNU3	moderate	Posttranslational Modification	[6]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[7]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Vinblastine	DM5TVS3	Approved	Histone H1.2 (H1-2) affects the response to substance of Vinblastine.	[43]
NVP-LAQ824	DM8JWNA	Phase 3	Histone H1.2 (H1-2) affects the response to substance of NVP-LAQ824.	[44]

2 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 H1.2 (H1-2).	[8]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Histone H1.2 (H1-2).	[33]

36 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 H1.2 (H1-2).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Histone H1.2 (H1-2).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Histone H1.2 (H1-2).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Histone H1.2 (H1-2).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Histone H1.2 (H1-2).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Histone H1.2 (H1-2).	[14]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Histone H1.2 (H1-2).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Histone H1.2 (H1-2).	[16]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Histone H1.2 (H1-2).	[17]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Histone H1.2 (H1-2).	[18]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Histone H1.2 (H1-2).	[19]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Histone H1.2 (H1-2).	[20]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Histone H1.2 (H1-2).	[21]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Histone H1.2 (H1-2).	[22]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Histone H1.2 (H1-2).	[23]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Histone H1.2 (H1-2).	[24]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Histone H1.2 (H1-2).	[25]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Histone H1.2 (H1-2).	[26]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of Histone H1.2 (H1-2).	[26]
Ibuprofen	DM8VCBE	Approved	Ibuprofen decreases the expression of Histone H1.2 (H1-2).	[26]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the expression of Histone H1.2 (H1-2).	[26]
Aminoglutethimide	DMWFHMZ	Approved	Aminoglutethimide increases the expression of Histone H1.2 (H1-2).	[27]
Vandetanib	DMRICNP	Approved	Vandetanib increases the expression of Histone H1.2 (H1-2).	[28]
Isoflavone	DM7U58J	Phase 4	Isoflavone affects the expression of Histone H1.2 (H1-2).	[29]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Histone H1.2 (H1-2).	[30]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Histone H1.2 (H1-2).	[31]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Histone H1.2 (H1-2).	[32]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Histone H1.2 (H1-2).	[34]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Histone H1.2 (H1-2).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Histone H1.2 (H1-2).	[36]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Histone H1.2 (H1-2).	[37]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Histone H1.2 (H1-2).	[38]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Histone H1.2 (H1-2).	[39]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Histone H1.2 (H1-2).	[40]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Histone H1.2 (H1-2).	[41]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of Histone H1.2 (H1-2).	[42]

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