Advances in the development of histone lysine demethylase inhibitors

Current Opinion in Pharmacology

Volumn 23, Issue 1, 2015, Pages 52-60

  Maes, Tamara ^a   Carceller, Elena ^a   Salas, Jordi ^a   Ortega, Alberto ^a   Buesa, Carlos ^a  

^a ORYZON GENOMICS   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

2 PHENYLCYCLOPROPYL 1 AMINE HYDROCHLORIDE; 4SC 202; DAMINOZIDE; EPT 103182; GSK 690; GSK J1; HISTONE DEMETHYLASE; HISTONE LYSINE DEMETHYLASE INHIBITOR; JMJD1C DEMETHYLASE; JMJD6 PROTEIN; KDM1A DEMETHYLASE; KDM1B DEMETHYLASE; KDM2A DEMETHYLASE; KDM3A DEMETHYLASE; KDM3B DEMETHYLASE; KDM4 DEMETHYLASE; KDM5 DEMETHYLASE; KDM6A DEMETHYLASE; KDM6B DEMETHYLASE; KDM6C DEMETHYLASE; KDM7A DEMETHYLASE; KDM8 DEMETHYLASE; ML 324; ORY 2001; OXYGENASE INHIBITOR; SP 2509; TRANYLCYPROMINE; UNCLASSIFIED DRUG; VORINOSTAT; BENZOIC ACID DERIVATIVE; CYCLOPROPANE DERIVATIVE; ENZYME INHIBITOR; GSK2879552; KDM1A PROTEIN, HUMAN;

DRUG DEVELOPMENT; DRUG STRUCTURE; ENZYME ACTIVITY; GENE EXPRESSION; GENETIC TRANSCRIPTION; HISTONE DEMETHYLATION; HISTONE MODIFICATION; PRIORITY JOURNAL; PROTEIN TARGETING; REVIEW; RNA TRANSLATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; ENZYMOLOGY; HUMAN; NEOPLASMS;

ANIMALS; BENZOATES; CYCLOPROPANES; ENZYME INHIBITORS; HISTONE DEMETHYLASES; HUMANS; NEOPLASMS;

EID: 84934966421     PISSN: 14714892     EISSN: 14714973     Source Type: Journal    
DOI: 10.1016/j.coph.2015.05.009     Document Type: Review

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55. Wang L, Chang J, Varghese D, Dellinger M, Kumar S, Best AM, Ruiz J, Bruick R, Peña-Llopis S, Xu J et al.: A small molecule modulates Jumonji histone demethylase activity and selectively inhibits cancer growth. Nat Commun 2013, 4:2035 http://dx.doi.org/10.1038/ncomms3035. The authors identified JIB-04 as an inhibitor of the Jumonji family of histone demethylases JIB-04 in a cell screen. Although the compound is a pan-KDM inhibitor it is interesting because it is not a competitive inhibitor of a-ketoglutarate, because it enters relatively well in cells, and displays selectivity inkilling certain tumor cells vs normal cells. The compound was also active in vivo in H358 an A549 xenograft models when administered i.p. at 110 mg/kg. Especially relevant but not available in the form of a published manuscript: The most advanced efforts on KDM inhibitors have been reported by Oryzon (ORY-1001), GSK (GSK2879552) and Epitherapeutics (EPT-103182). These advances are cited in the text but they are not yet available in the form of a regular manuscript on the development of the cited compounds.