CG-1521

CG-1521 is a histone deacetylase (HDAC) inhibitor that stabilizes Ac-Lys373P53, increases P21 levels, and promotes the degradation of HDAC2. It suppresses proliferation, induces cell cycle arrest, and triggers apoptosis. Additionally, CG-1521 facilitates the translocation of Bax to the mitochondria and its cleavage. It also downregulates the expression of KIF4, Aurora B, Nek2 proteins, and DNA synthesis. CG-1521 is applicable in research on prostate cancer and inflammatory breast cancer.

CG-1521 at a concentration of 7.5 μM for 0-72 hours elevates p21, Gadd45a, and Wee1 in LNCaP cells, while reducing cyclin B1, Cks2, Cdc20, Plk1, Stk6, and Kntc2 levels. The compound also upregulates pro-apoptotic genes (Gadd153, Bnip3, Bnip3L, Pig3, Gdf15, p21B) and diminishes the anti-apoptotic gene survivin in the same cells. Additionally, CG-1521 (0-10 μM for 48 h) induces dose-dependent growth inhibition in SUM149PT and SUM190PT IBC cells. It promotes G1 phase arrest and apoptosis with altered mRNA expression in SUM149PT cells when used at 7.5 μM for 24-48 hours. In SUM190PT cells, CG-1521 at 5 μM for 24-48 hours leads to G0/G1 arrest, apoptosis, and mRNA regulation. Prolonged exposure (7.5 μM for 48 h) in SUM149PT cells causes elongation of midzone structures and consequent failure in cytokinesis. The expression of KIF4 protein decreases after 48-72 hours, with a slight reduction in Aurora B protein noted. Notably, 7.5 μM for 24-48 hours subtly decreases Nek2 protein expression in SUM149PT cells at 24 h, with recovery by 48 h. CG-1521 at 1-10 μM over 0-96 hours inhibits proliferation and induces G2/M phase arrest and apoptosis in LNCaP cells, but only G2/M arrest in PC-3 cells without apoptosis. It induces sustained hyperacetylation of histones H3 and H4, while decreasing HDAC2 protein levels in LNCaP cells within 1-24 hours. Moreover, it stabilizes acetylated p53 at Lys373, increasing total p53 and P21 levels over 1-48 hours. Lastly, CG-1521 prompts the translocation of Bax from the cytosol to mitochondria in LNCaP cells, followed by its cleavage to t-Bax.