OBP-801

Spiruchostatin A is a potent HDAC inhibitor with an IC50 value of 2 nM. Spiruchostatin A can induce apoptosis, has antitumor activity and may be used in leukemia studies[1][2].

Research Areas >> Cancer

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

Signaling Pathways >> Epigenetics >> HDAC

Spiruchostatin A (3-100 nM, 12 or 24 h) can induce apoptosis in a dose-dependent manner in U937 cells and induce apoptosis in human myelomonocytic lymphoma cell in a time- and dose-dependent manner[1]. Spiruchostatin A (30 nM, 0-24 h) increases in the acetylated histone H3 and H4 levels in a time-dependent manner[1]. Apoptosis Analysis[1] Cell Line: U937 cells, human myelomonocytic lymphoma cells Concentration: 3-100 nM Incubation Time: 12 or 24 h Result: Significantly increased in intracellular reactive oxygen species (ROS) formation. Induced caspase activation and increased the cleaved form of caspase-3 at 30 nM. Induced cytochrome-c release from mitochondria to cytosol at 30 nM. Cell Cycle Analysis[1] Cell Line: U937 cells Concentration: 30 nM Incubation Time: 24 h Result: Increased the percentage of sub-G1 cells from 2.3% to 27%.

Spiruchostatin A (YM753) (i.v., 3 mg/kg, once) significantly inhibits tumor growth via accumulation of acetylated histones and p21WAF1/Cip1 protein in the WiDr xenograft model[2]. Animal Model: WiDr xenograft nude mice model bearing tumors[2] Dosage: 3 mg/kg Administration: A single intravenous administration Result: Increased acetylation of histones H3 and H4 even after 72 hours of administration. Showed that YM753 is a prodrug that is reduced to RedYM in tumor cells. Plasma concentrations of YM753 were 558 nM at 3 min and 15 nM at 15 min, in addition, plasma levels of RedYM were 65 nM at 3 min and 1.3 nM at 15 min.