Journal article icon

Journal article

C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-ones: Studies towards the identification of potent, cell penetrant Jumonji C domain containing histone lysine demethylase 4 subfamily (KDM4) inhibitors, compound profiling in cell-based target engagement assays

Abstract:

Residues in the histone substrate binding sites that differ between the KDM4 and KDM5 subfamilies were identified. Subsequently, a C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-one series was designed to rationally exploit these residue differences between the histone substrate binding sites in order to improve affinity for the KDM4-subfamily over KDM5-subfamily enzymes. In particular, residues E169 and V313 (KDM4A numbering) were targeted. Additionally, conformational restriction of the flexib...

Expand abstract
Publication status:
Published
Peer review status:
Peer reviewed

Actions


Access Document


Files:
Publisher copy:
10.1016/j.ejmech.2019.05.041

Authors


Expand authors...
Publisher:
Elsevier Publisher's website
Journal:
European Journal of Medicinal Chemistry Journal website
Volume:
177
Pages:
316-337
Publication date:
2019-05-17
Acceptance date:
2019-05-14
DOI:
EISSN:
1768-3254
ISSN:
0223-5234
Pmid:
31158747
Source identifiers:
1007227

Terms of use


Views and Downloads






If you are the owner of this record, you can report an update to it here: Report update to this record

TO TOP