CG-200745

CG-200745 is a potent HDAC inhibitor, with IC50s of <3 μM for sensitive non-small cell lung cancer (NSCLC) cell lines. CG-200745 induces the accumulation of p53, promotes p53-dependent transactivation, and enhances the expression of proteins encoded by p53 target genes, MDM2 and p21 (Waf1/Cip1) in human prostate cancer cells[1]. CG-200745 attenuates phosphorylation of p38 MAPK in kidneys and it has a renoprotective effect by suppressing renal fibrosis and inflammation in a unilateral ureteral obstruction (UUO) mouse model[2].

Research Areas >> Cancer

Signaling Pathways >> Apoptosis >> MDM-2/p53

Signaling Pathways >> MAPK/ERK Pathway >> p38 MAPK

Signaling Pathways >> Cell Cycle/DNA Damage >> HDAC

Signaling Pathways >> Epigenetics >> HDAC

HDAC

p53

p38 MAP kinase

CG-200745 (0-10 μM; 48 hours) reduces the Calu6 cells proliferation to 40% of untreated cells[1]. CG-200745 (3 μM; 1-24 hours) significantly increases Calu6 cells proportion in G2/M phase (69%)[1]. CG-200745 (0-10 μM; 1-24 hours) treatment with low concentration significantly increases the acetylation of histone H3 and H4 in Calu6 cells at various sites in a time-dependent manner up to 24 hours after treatment[1]. Cell Proliferation Assay[1] Cell Line: Calu6 cells Concentration: 0-10 μM Incubation Time: 48 hours Result: Reduced the cell proliferation to 40% of untreated cells. Cell Cycle Analysis[1] Cell Line: Calu6 cells Concentration: 3 μM Incubation Time: 1, 8, 12, 24 hours Result: Increased significantly cell proportion in G2/M phase (69%). Western Blot Analysis[1] Cell Line: Calu6 cells Concentration: 0-10 μM Incubation Time: 1, 4, 8, 12, 24 hours Result: Increased the acetylation of histone H3 and H4 at various sites in a time-dependent manner.

CG-200745 (p.o.; 30 mg/kg/day; for 7 days) attenuates oxidative stress, inflammatory cytokines, and adhesion molecules in UUO kidneys[2]. Animal Model: Male 8-week-old C57BL/6 J mice weighing 20~22 g of unilateral ureteral obstruction (UUO)[2] Dosage: 30 mg/kg Administration: P.o.; daily; for 7 days Result: Attenuated oxidative stress, inflammatory cytokines and adhesion molecules in UUO kidneys.

[1]. Chun SM, et al. Epigenetic modulation with HDAC inhibitor CG200745 induces anti-proliferation in non-small cell lung cancer cells. PLoS One. 2015 Mar 17;10(3):e0119379.

[2]. Choi HS, et al. Histone deacetylase inhibitor, CG200745 attenuates renal fibrosis in obstructive kidney disease. Sci Rep. 2018 Aug 1;8(1):11546.