Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTZHPB8)

• DTT Name: Lysine-specific demethylase 4A (KDM4A)
• Synonyms: KIAA0677; Jumonji domain-containing protein 2A; JmjC domain-containing histone demethylation protein 3A; JMJD2A; JMJD2; JHDM3A
• Gene Name: KDM4A
• DTT Type: Patented-recorded target; [1]
• BioChemical Class: Paired donor oxygen oxidoreductase
• UniProt ID: KDM4A_HUMAN
• TTD ID: T18904
• EC Number: EC 1.14.11.-
• Sequence:
  MASESETLNPSARIMTFYPTMEEFRNFSRYIAYIESQGAHRAGLAKVVPPKEWKPRASYD
  DIDDLVIPAPIQQLVTGQSGLFTQYNIQKKAMTVREFRKIANSDKYCTPRYSEFEELERK
  YWKNLTFNPPIYGADVNGTLYEKHVDEWNIGRLRTILDLVEKESGITIEGVNTPYLYFGM
  WKTSFAWHTEDMDLYSINYLHFGEPKSWYSVPPEHGKRLERLAKGFFPGSAQSCEAFLRH
  KMTLISPLMLKKYGIPFDKVTQEAGEFMITFPYGYHAGFNHGFNCAESTNFATRRWIEYG
  KQAVLCSCRKDMVKISMDVFVRKFQPERYKLWKAGKDNTVIDHTLPTPEAAEFLKESELP
  PRAGNEEECPEEDMEGVEDGEEGDLKTSLAKHRIGTKRHRVCLEIPQEVSQSELFPKEDL
  SSEQYEMTECPAALAPVRPTHSSVRQVEDGLTFPDYSDSTEVKFEELKNVKLEEEDEEEE
  QAAAALDLSVNPASVGGRLVFSGSKKKSSSSLGSGSSRDSISSDSETSEPLSCRAQGQTG
  VLTVHSYAKGDGRVTVGEPCTRKKGSAARSFSERELAEVADEYMFSLEENKKSKGRRQPL
  SKLPRHHPLVLQECVSDDETSEQLTPEEEAEETEAWAKPLSQLWQNRPPNFEAEKEFNET
  MAQQAPHCAVCMIFQTYHQVEFGGFNQNCGNASDLAPQKQRTKPLIPEMCFTSTGCSTDI
  NLSTPYLEEDGTSILVSCKKCSVRVHASCYGVPPAKASEDWMCSRCSANALEEDCCLCSL
  RGGALQRANDDRWVHVSCAVAILEARFVNIAERSPVDVSKIPLPRFKLKCIFCKKRRKRT
  AGCCVQCSHGRCPTAFHVSCAQAAGVMMQPDDWPFVVFITCFRHKIPNLERAKGALQSIT
  AGQKVISKHKNGRFYQCEVVRLTTETFYEVNFDDGSFSDNLYPEDIVSQDCLQFGPPAEG
  EVVQVRWTDGQVYGAKFVASHPIQMYQVEFEDGSQLVVKRDDVYTLDEELPKRVKSRLSV
  ASDMRFNEIFTEKEVKQEKKRQRVINSRYREDYIEPALYRAIME
• Function: Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. Participates in transcriptional repression of ASCL2 and E2F-responsive promoters via the recruitment of histone deacetylases and NCOR1, respectively.
• Reactome Pathway:
  Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks (R-HSA-5693565)
  NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux (R-HSA-9029569)
  HDMs demethylate histones (R-HSA-3214842)
• BioCyc Pathway: MetaCyc:ENSG00000066135-MON

Molecular Interaction Atlas (MIA) of This DTT

11 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Disulfiram analog 1	DMOEFD3	N. A.	N. A.	Patented	[1]
Disulfiram analog 2	DMOMGU5	N. A.	N. A.	Patented	[1]
Heteroaryl-cyclopropylamine derivative 4	DMMU01R	N. A.	N. A.	Patented	[2]
Hydroxamate analog 1	DMGATHZ	N. A.	N. A.	Patented	[1]
N-(2-phenylcyclopropyl) amino acid derivative 1	DMH7T8C	N. A.	N. A.	Patented	[2]
PMID25468267-Compound-46	DMSKCEH	N. A.	N. A.	Patented	[1]
PMID27019002-Compound-21b	DMMC31N	N. A.	N. A.	Patented	[2]
PMID27019002-Compound-21c	DMWZOKP	N. A.	N. A.	Patented	[2]
Selenium compound 1	DM9C5Z8	N. A.	N. A.	Patented	[1]
Selenium compound 2	DMLWIJ7	N. A.	N. A.	Patented	[1]
Selenium compound 3	DMQ5AJ6	N. A.	N. A.	Patented	[1]

References

• [1] KDM4 histone demethylase inhibitors for anti-cancer agents: a patent review.Expert Opin Ther Pat. 2015 Feb;25(2):135-44.
• [2] LSD1 inhibitors: a patent review (2010-2015).Expert Opin Ther Pat. 2016 May;26(5):565-80.