Thaspine acetate is a potent topoisomerase IB inhibitor. Taspine downregulates VEGF expression and inhibits proliferation of vascular endothelial cells through PI3 kinase and MAP kinase signaling pathways.
The Survival of Motor Neurons (SMN) protein participates in RNA splicing. Decreases in SMN, typically a consequence of defects in the smn1 gene, result in the death of motor neurons and lead to the neurodegenerative disease, spinal muscular atrophy (SMA). Cuspin-1 is a small molecule upregulator of SMN that has been shown in vitro to increase levels of SMN in SMA patient fibroblasts by 50% at 18 μM. Its mechanism of action is thought to involve increased phosphorylation of ERK to initiate Ras-Raf-MEK signaling, which results in an increased rate of SMN translation.
Methylspinazarin is a naphthoquinone bacterial metabolite that has been found in Streptomyces and is an inhibitor of catechol O-methyltransferase (COMT; IC50 = 0.8 μg ml).1 It is selective for COMT over tyrosine hydroxylase, DOPA decarboxylase, and dopamine-β-hydroxylase at 100 μg ml. Methylspinazarin decreases blood pressure in spontaneously hypertensive rats when administered at a dose of 50 mg kg. |1. Chimura, H., Sawa, T., Takita, T., et al. Methylspinazarin and dihydromethylspinazarin, gatechol-O-methyl transerfase inhibitors produced by Streptomyces. J. Antibiot. 26(2), 112-114 (1973).