Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5P1UPY)

• DOT Name: Lysine-specific demethylase 4B (KDM4B)
• Synonyms: EC 1.14.11.66; JmjC domain-containing histone demethylation protein 3B; Jumonji domain-containing protein 2B; -trimethyl-L-lysine(9) demethylase 4B
• Gene Name: KDM4B
• Related Disease:
  Adenocarcinoma
  Colorectal neoplasm
  Medulloblastoma
  Brain disease
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Castration-resistant prostate carcinoma
  Cervical Intraepithelial neoplasia
  Colon cancer
  Colon carcinoma
  Complex neurodevelopmental disorder
  Endometrial cancer
  Endometrial carcinoma
  Epithelial ovarian cancer
  Fatty liver disease
  Hyperlipidemia
  Intellectual developmental disorder, autosomal dominant 65
  Lung cancer
  Lung carcinoma
  Metabolic bone disease
  Neoplasm
  Non-small-cell lung cancer
  Obesity
  Osteoporosis
  Ovarian cancer
  Ovarian neoplasm
  Periodontal disease
  Prostate cancer
  Prostate carcinoma
  Hepatocellular carcinoma
  Melanoma
  Urinary bladder cancer
  Syndromic intellectual disability
  Advanced cancer
  Bone osteosarcoma
  Colorectal carcinoma
  Lung adenocarcinoma
  Metastatic malignant neoplasm
  Neuroblastoma
  Osteosarcoma
  Systemic lupus erythematosus
• UniProt ID: KDM4B_HUMAN
• PDB ID: 4LXL; 4UC4; 7JM5
• EC Number: 1.14.11.66
• Pfam ID: PF02373 ; PF02375 ; PF13831 ; PF18104 ; PF13832
• Sequence:
  MGSEDHGAQNPSCKIMTFRPTMEEFKDFNKYVAYIESQGAHRAGLAKIIPPKEWKPRQTY
  DDIDDVVIPAPIQQVVTGQSGLFTQYNIQKKAMTVGEYRRLANSEKYCTPRHQDFDDLER
  KYWKNLTFVSPIYGADISGSLYDDDVAQWNIGSLRTILDMVERECGTIIEGVNTPYLYFG
  MWKTTFAWHTEDMDLYSINYLHFGEPKSWYAIPPEHGKRLERLAIGFFPGSSQGCDAFLR
  HKMTLISPIILKKYGIPFSRITQEAGEFMITFPYGYHAGFNHGFNCAESTNFATLRWIDY
  GKVATQCTCRKDMVKISMDVFVRILQPERYELWKQGKDLTVLDHTRPTALTSPELSSWSA
  SRASLKAKLLRRSHRKRSQPKKPKPEDPKFPGEGTAGAALLEEAGGSVKEEAGPEVDPEE
  EEEEPQPLPHGREAEGAEEDGRGKLRPTKAKSERKKKSFGLLPPQLPPPPAHFPSEEALW
  LPSPLEPPVLGPGPAAMEESPLPAPLNVVPPEVPSEELEAKPRPIIPMLYVVPRPGKAAF
  NQEHVSCQQAFEHFAQKGPTWKEPVSPMELTGPEDGAASSGAGRMETKARAGEGQAPSTF
  SKLKMEIKKSRRHPLGRPPTRSPLSVVKQEASSDEEASPFSGEEDVSDPDALRPLLSLQW
  KNRAASFQAERKFNAAAARTEPYCAICTLFYPYCQALQTEKEAPIASLGKGCPATLPSKS
  RQKTRPLIPEMCFTSGGENTEPLPANSYIGDDGTSPLIACGKCCLQVHASCYGIRPELVN
  EGWTCSRCAAHAWTAECCLCNLRGGALQMTTDRRWIHVICAIAVPEARFLNVIERHPVDI
  SAIPEQRWKLKCVYCRKRMKKVSGACIQCSYEHCSTSFHVTCAHAAGVLMEPDDWPYVVS
  ITCLKHKSGGHAVQLLRAVSLGQVVITKNRNGLYYRCRVIGAASQTCYEVNFDDGSYSDN
  LYPESITSRDCVQLGPPSEGELVELRWTDGNLYKAKFISSVTSHIYQVEFEDGSQLTVKR
  GDIFTLEEELPKRVRSRLSLSTGAPQEPAFSGEEAKAAKRPRVGTPLATEDSGRSQDYVA
  FVESLLQVQGRPGAPF
• Function: Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27', H3 'Lys-36' nor H4 'Lys-20'. Only able to demethylate trimethylated H3 'Lys-9', with a weaker activity than KDM4A, KDM4C and KDM4D. Demethylation of Lys residue generates formaldehyde and succinate. Plays a critical role in the development of the central nervous system (CNS).
• Reactome Pathway:
  Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks (R-HSA-5693565)
  Estrogen-dependent gene expression (R-HSA-9018519)
  HDMs demethylate histones (R-HSA-3214842)
• BioCyc Pathway: MetaCyc:ENSG00000127663-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Definitive	Altered Expression	[1]
Colorectal neoplasm	DISR1UCN	Definitive	Altered Expression	[1]
Medulloblastoma	DISZD2ZL	Definitive	Biomarker	[2]
Brain disease	DIS6ZC3X	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[4]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[5]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Biomarker	[6]
Cervical Intraepithelial neoplasia	DISXP757	Strong	Altered Expression	[5]
Colon cancer	DISVC52G	Strong	Biomarker	[7]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[7]
Complex neurodevelopmental disorder	DISB9AFI	Strong	Autosomal dominant	[8]
Endometrial cancer	DISW0LMR	Strong	Altered Expression	[9]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[9]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[10]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[11]
Hyperlipidemia	DIS61J3S	Strong	Biomarker	[12]
Intellectual developmental disorder, autosomal dominant 65	DISW401P	Strong	Autosomal dominant	[13]
Lung cancer	DISCM4YA	Strong	Biomarker	[14]
Lung carcinoma	DISTR26C	Strong	Biomarker	[14]
Metabolic bone disease	DISO7RI8	Strong	Biomarker	[15]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[16]
Obesity	DIS47Y1K	Strong	Biomarker	[12]
Osteoporosis	DISF2JE0	Strong	Biomarker	[15]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[10]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[10]
Periodontal disease	DISJQHVN	Strong	Biomarker	[17]
Prostate cancer	DISF190Y	Strong	Altered Expression	[6]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[6]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[18]
Melanoma	DIS1RRCY	moderate	Biomarker	[19]
Urinary bladder cancer	DISDV4T7	moderate	Altered Expression	[20]
Syndromic intellectual disability	DISH7SDF	Supportive	Autosomal dominant	[8]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[21]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[22]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[23]
Lung adenocarcinoma	DISD51WR	Limited	Biomarker	[14]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[24]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[25]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[22]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Lysine-specific demethylase 4B (KDM4B).	[27]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Lysine-specific demethylase 4B (KDM4B).	[28]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Lysine-specific demethylase 4B (KDM4B).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Lysine-specific demethylase 4B (KDM4B).	[40]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Lysine-specific demethylase 4B (KDM4B).	[42]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Lysine-specific demethylase 4B (KDM4B).	[43]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Lysine-specific demethylase 4B (KDM4B).	[46]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Lysine-specific demethylase 4B (KDM4B).	[29]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Lysine-specific demethylase 4B (KDM4B).	[30]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Lysine-specific demethylase 4B (KDM4B).	[31]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Lysine-specific demethylase 4B (KDM4B).	[33]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Lysine-specific demethylase 4B (KDM4B).	[34]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Lysine-specific demethylase 4B (KDM4B).	[35]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Lysine-specific demethylase 4B (KDM4B).	[36]
Nitric Oxide	DM1RBYG	Approved	Nitric Oxide increases the expression of Lysine-specific demethylase 4B (KDM4B).	[37]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Lysine-specific demethylase 4B (KDM4B).	[38]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Lysine-specific demethylase 4B (KDM4B).	[39]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Lysine-specific demethylase 4B (KDM4B).	[41]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Lysine-specific demethylase 4B (KDM4B).	[44]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Lysine-specific demethylase 4B (KDM4B).	[45]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Lysine-specific demethylase 4B (KDM4B).	[47]

References

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