Biological Activity
gsk j5 is an inactive isomer of gsk j4 and a cell-permeable ester derivative of inactive control gsk j2. lysine-specific demethylase 6b (kdm6b), also known as jumonji domain-containing protein d3 (jmjd3), was overexpressed in patients with aml and these patients have a poor prognosis. kdm6b-specific pharmacological inhibitor gsk-j4 had a significant anti-proliferative effect in aml cell lines and freshly isolated bm monocytes (mncs) from aml patients, while h3k27me3 levels were also increasing. gsk-j4 also caused apoptosis and cell cycle arrest in vitro, and reduced tumor burden in vivo in aml xenograft mouse models. it is worth noting that injection of gsk-j4 attenuated disease progression in a human aml xenograft mouse model. treatment with gsk-j4 mainly resulted in downregulation of dna replication and cell cycle-related pathways, and prevents the expression of hox, a key cancer gene. chip-qpcr verified the increased h3k27me3 enrichment in the hox gene transcription initiation site [1].[1]. li y, zhang m, sheng m, zhang p, chen z, xing w, bai j, cheng t, yang fc, zhou y. therapeutic potential of gsk-j4, a histone demethylase kdm6b/jmjd3 inhibitor, for acute myeloid leukemia. j cancer res clin oncol. 2018 jun;144(6):1065-1077. doi: 10.1007/s00432-018-2631-7. epub 2018 mar 28. pubmed pmid: 29594337; pubmed central pmcid: pmc5948279.
