Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTIG67W)

• DTT Name: Lysine-specific demethylase 5A (KDM5A)
• Synonyms: Retinoblastoma-binding protein 2; RBP2; RBBP2; RBBP-2; Jumonji/ARID domain-containing protein 1A; JARID1A; Histone demethylase JARID1A
• Gene Name: KDM5A
• DTT Type: Patented-recorded target; [1]
• BioChemical Class: Paired donor oxygen oxidoreductase
• UniProt ID: KDM5A_HUMAN
• TTD ID: T28052
• EC Number: EC 1.14.11.-
• Sequence:
  MAGVGPGGYAAEFVPPPECPVFEPSWEEFTDPLSFIGRIRPLAEKTGICKIRPPKDWQPP
  FACEVKSFRFTPRVQRLNELEAMTRVRLDFLDQLAKFWELQGSTLKIPVVERKILDLYAL
  SKIVASKGGFEMVTKEKKWSKVGSRLGYLPGKGTGSLLKSHYERILYPYELFQSGVSLMG
  VQMPNLDLKEKVEPEVLSTDTQTSPEPGTRMNILPKRTRRVKTQSESGDVSRNTELKKLQ
  IFGAGPKVVGLAMGTKDKEDEVTRRRKVTNRSDAFNMQMRQRKGTLSVNFVDLYVCMFCG
  RGNNEDKLLLCDGCDDSYHTFCLIPPLPDVPKGDWRCPKCVAEECSKPREAFGFEQAVRE
  YTLQSFGEMADNFKSDYFNMPVHMVPTELVEKEFWRLVSSIEEDVIVEYGADISSKDFGS
  GFPVKDGRRKILPEEEEYALSGWNLNNMPVLEQSVLAHINVDISGMKVPWLYVGMCFSSF
  CWHIEDHWSYSINYLHWGEPKTWYGVPSHAAEQLEEVMRELAPELFESQPDLLHQLVTIM
  NPNVLMEHGVPVYRTNQCAGEFVVTFPRAYHSGFNQGYNFAEAVNFCTADWLPIGRQCVN
  HYRRLRRHCVFSHEELIFKMAADPECLDVGLAAMVCKELTLMTEEETRLRESVVQMGVLM
  SEEEVFELVPDDERQCSACRTTCFLSALTCSCNPERLVCLYHPTDLCPCPMQKKCLRYRY
  PLEDLPSLLYGVKVRAQSYDTWVSRVTEALSANFNHKKDLIELRVMLEDAEDRKYPENDL
  FRKLRDAVKEAETCASVAQLLLSKKQKHRQSPDSGRTRTKLTVEELKAFVQQLFSLPCVI
  SQARQVKNLLDDVEEFHERAQEAMMDETPDSSKLQMLIDMGSSLYVELPELPRLKQELQQ
  ARWLDEVRLTLSDPQQVTLDVMKKLIDSGVGLAPHHAVEKAMAELQELLTVSERWEEKAK
  VCLQARPRHSVASLESIVNEAKNIPAFLPNVLSLKEALQKAREWTAKVEAIQSGSNYAYL
  EQLESLSAKGRPIPVRLEALPQVESQVAAARAWRERTGRTFLKKNSSHTLLQVLSPRTDI
  GVYGSGKNRRKKVKELIEKEKEKDLDLEPLSDLEEGLEETRDTAMVVAVFKEREQKEIEA
  MHSLRAANLAKMTMVDRIEEVKFCICRKTASGFMLQCELCKDWFHNSCVPLPKSSSQKKG
  SSWQAKEVKFLCPLCMRSRRPRLETILSLLVSLQKLPVRLPEGEALQCLTERAMSWQDRA
  RQALATDELSSALAKLSVLSQRMVEQAAREKTEKIISAELQKAAANPDLQGHLPSFQQSA
  FNRVVSSVSSSPRQTMDYDDEETDSDEDIRETYGYDMKDTASVKSSSSLEPNLFCDEEIP
  IKSEEVVTHMWTAPSFCAEHAYSSASKSCSQGSSTPRKQPRKSPLVPRSLEPPVLELSPG
  AKAQLEELMMVGDLLEVSLDETQHIWRILQATHPPSEDRFLHIMEDDSMEEKPLKVKGKD
  SSEKKRKRKLEKVEQLFGEGKQKSKELKKMDKPRKKKLKLGADKSKELNKLAKKLAKEEE
  RKKKKEKAAAAKVELVKESTEKKREKKVLDIPSKYDWSGAEESDDENAVCAAQNCQRPCK
  DKVDWVQCDGGCDEWFHQVCVGVSPEMAENEDYICINCAKKQGPVSPGPAPPPSFIMSYK
  LPMEDLKETS
• Function: Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. Regulates specific gene transcription through DNA-binding on 5'-CCGCCC-3' motif. May stimulate transcription mediated by nuclear receptors. Involved in transcriptional regulation of Hox proteins during cell differentiation. May participate in transcriptional repression of cytokines such as CXCL12. Plays a role in the regulation of the circadian rhythm and in maintaining the normal periodicity of the circadian clock. In a histone demethylase-independent manner, acts as a coactivator of the CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER1/2 and other clock-controlled genes and increases histone acetylation at PER1/2 promoters by inhibiting the activity of HDAC1. Seems to act as a transcriptional corepressor for some genes such as MT1F and to favor the proliferation of cancer cells. Histone demethylase that specifically demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code.
• Reactome Pathway: HDMs demethylate histones (R-HSA-3214842)
• BioCyc Pathway: MetaCyc:ENSG00000073614-MON

Molecular Interaction Atlas (MIA) of This DTT

20 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1190312-92-5	DMHNPSO	N. A.	N. A.	Patented	[2]
6EP	DMN082G	N. A.	N. A.	Patented	[3]
AKOS020330481	DMWHN1O	N. A.	N. A.	Patented	[4]
AKOS020330656	DMNIE4M	N. A.	N. A.	Patented	[5]
BDBM50158703	DMS7ZLK	N. A.	N. A.	Patented	[3]
BDBM50158755	DMYJF70	N. A.	N. A.	Patented	[6]
BDBM50158791	DMU07MO	N. A.	N. A.	Patented	[7]
BDBM50158794	DMWJZU9	N. A.	N. A.	Patented	[8]
BDBM50158803	DMTWI1H	N. A.	N. A.	Patented	[9]
NCGC00381656-01	DMEU12W	N. A.	N. A.	Patented	[10]
US10022354, Example 151	DMVCWXD	N. A.	N. A.	Patented	[11]
US10022354, Example 152	DMGDZLP	N. A.	N. A.	Patented	[11]
US10022354, Example 5	DMIAGPX	N. A.	N. A.	Patented	[11]
US10040779, Example 1	DMLMV1Y	N. A.	N. A.	Patented	[8]
US10040779, Example 4	DMWDGCH	N. A.	N. A.	Patented	[8]
US10174026, Example 2	DMSYRI3	N. A.	N. A.	Patented	[2]
US10174026, Example 99	DMJKTYW	N. A.	N. A.	Patented	[2]
US9611221, Example 9	DMSD354	N. A.	N. A.	Patented	[4]
US9714230, 12	DMEB59T	N. A.	N. A.	Patented	[3]
US9714230, 46	DMPZS16	N. A.	N. A.	Patented	[12]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PBIT	DM8Q54I	Discovery agent	N.A.	Investigative	[1]

References

• [1] Identification of small molecule inhibitors of Jumonji AT-rich interactive domain 1B (JARID1B) histone demethylase by a sensitive high throughput screen. J Biol Chem. 2013 Mar 29;288(13):9408-17.
• [2] Histone demethylase inhibitors. US10174026.
• [3] Histone demethylase inhibitors. US9714230.
• [4] Histone demethylase inhibitors. US9611221.
• [5] Histone demethylase inhibitors. US10179769.
• [6] Histone demethylase inhibitors. US10173996.
• [7] Histone demethylase inhibitors. US9725441.
• [8] Histone demethylase inhibitors. US10040779.
• [9] Histone demethylase inhibitors. US9617242.
• [10] Histone demethylase inhibitors. US9738637.
• [11] IRE-1 inhibitors
• [12] Histone demethylase inhibitors. US9604961.