| SB939 is a potent novel HDACs inhibitor with IC50 values ranging from 40 to 140 nM. SB939 significantly inhibits HDAC class I isoenzymes HDAC1, HDAC2, HDAC3 and HDAC8 with IC50 values of 49, 96, 43 and 140 nM, respectively. SB939 inhibits HDAC class II isoenzymes HDAC4, HDAC5, HDAC7, HDAC9 and HDAC10 with IC50 values of 56, 47, 137, 70 and 40 nM, respectively. SB939 also potently inhibits HDAC class IV enzyme HDAC11 with IC50 value of 93 nM. SB939 inhibits HDACs class I, II, and IV isolated enzymes with a Ki value of 19 to 48 nM (class I), 16 to 247 nM (class II), and 43 nM (class IV). SB939 significantly inhibits the growth of colon cancer cell line Colo205, ovarian cancer cell line A2780, prostate cancer cell line PC3 and breast cancer cell line MCF7 with IC50 values of 540, 480, 340 and 510 nM, respectively. In addition, SB939 also inhibits the growth of lung cancer cell line (NSCL) NCI-H460, liver cancer cell line HEP3B, pancreas cancer cell line MiaPaCa and melanoma cell line MDA-MB435 with IC50 values of 1.29, 1.23, 0.93 and 0.76 µM, respectively. In a xenograft model of human colorectal cancer (HCT-116) in vivo, SB939 treatment (100 mg/kg) has a tumor growth inhibition of 94% versus 48% for suberoylanilide hydroxamic acid (SAHA). Furthermore, in APCmin mice, a genetic mouse model of early-stage colon cancer, SB939 (50 and 75 mg/kg) inhibits adenoma formation, hemocult scores, and increases hematocrit values more effectively than 5-fluorouracil.[1] In liver tissue of HCT-116 xenografted BALB/c nude mice, SB939 treatment (25-50 mg/kg) leads to dose-dependent and significant increases in acH3.[2] |
