Uses
Butyrolactone I is one of a family of three butyrolactones isolated from Aspergillus fumigatus, first reported in 1983. Butyrolactone I exhibits antitumor activity, inhibiting the cell cycle at the G1/S and G2/M transitions. Butyrolactone I is a selective inhibitor of cyclin-dependent kinases CDK1/cyclin B, CDK2 and CDK5, and is an important bioprobe for understanding the cellular roles of CDKs.
Biological Activity
Cell permeable: yes', 'Primary Target
p34cdk1/cyclinB', 'Product does not compete with ATP.', 'Reversible: no', 'Target IC50: 680 nM against Cdk1
Enzyme inhibitor
This natural product (FW = 424.45 g/mol), first identified in species of Aspergillus and named systematically as 2,5-dihydro-4-hydroxy 2-([4- hydroxy-3-(3-methyl-2-butenyl)phenyl]methyl)-3-(4-hydroxyphenyl)-5-oxo- 2-furancarboxylic acid methyl ester, competes with ATP in cyclindependent kinase reactions. The IC50 values for these kinases are typically 0.6-1.5 μM. Butyrolactone I also inhibits cell proliferation by the inhibiting pRb phosphorylation in IMR32 cells, causing both G1 and G2 arrest and stimulating apoptosis. Target(s): cyclin-dependent kinases 1 and 2; cdk5; protein kinase C; protein kinase A; MAP kinase; casein kinase II; [tau protein] kinase.
in vivo
Butyrolactone-I (1-5 mg/kg, p.o., 14 days) ameliorates heat-stress-induced apoptosis in mice through the ROS/PERK/CHOP signaling pathway[3].
Butyrolactone-I (1-5 mg/kg, p.o., 14 days) alleviates intestinal barrier damage caused by DSS through regulating lactobacillus johnsonii and its metabolites in mice[6].
Butyrolactone I (10-40 mg/kg, p.o., from the 17th week to 24th week) attenuates inflammation in murine NASH by inhibiting the NF-κB signaling pathway[7].
| Animal Model: | Male C57BL/6J mice (heat-stressed)[3] |
| Dosage: | 1, 5 mg/kg |
| Administration: | Oral gavage (p.o.), 14 days |
| Result: | Downregulated HSP70 mRNA and mitigated weight loss.
Returned water intake and body temperature to normal levels.
Increased colon length.
Decreased Bax mRNA.
Inhibited the increases in the ROS and MDA levels.
Inhibited endoplasmic reticulum stress (ERS).
Inhibited p-PERK/PERK, p-eIF2α/eIF2α, ATF4, and CHOP.
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