D-4-6

Amino Acid Sequence

3D Structure (/structures/AF-P10275-F1-model_v6.cif)

Function

Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation. Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3

Description

We evaluated the ability of all compounds to induce AR degradation in LNCaP cells (human prostate cancer cells with AR high expression) at 5 μM with a 24 h treatment time by Western Blot. The smaller the ratio of AR protein content to the control group after drug treatment, the stronger the protein degradation ability of the drug. As shown in Fig. 6, a few of the 48 compounds showed good AR protein degradation ability. Compound D-3–6, D-4–6 and D-B-8 showed more than 50 % degrada tion capacity of AR protein, which were 55 %, 57 % and 58 % respectively.

Description

5) Compound D-3–6 and D-4–6 showed moderate AR degradation effect and anti-prostate cancer activity against LNCaP cells with IC50 of 5.11 μM and 4.77 μM respectively, which was superior to enzalutamide.