[CDK and MMP inhibitors].

Abstract

CDK inhibitor, Butyrolactone I inhibited CDK1, 2 and 5 in CDKs. In syncronized human lung fibroblast WI38 cells, it inhibited G1/S transition by inhibiting the phosphorylation of RB protein and G2/M transition by inhibiting the phosphorylation of H1 histone. Also, it selectively inhibited the initiation of DNA replication. The MMP inhibitor, BE16627B, reversively inhibited metalloproteinases including MMPs. It showed the MMP-dependent inhibition of the growth and metastasis of human tumor cells in nude mice without any cytotoxicity and severe side effects. The MMP inhibitor, Marimastat, showed remarkable prolongation of the life span of patients with pancreatic tumors in clinical trials.

• Authors: A Okuyama, T Akiyama, M Nakajima
• Journal: Gan to kagaku ryoho. Cancer & chemotherapy (Gan To Kagaku Ryoho) Vol. 24 Issue 11 Pg. 1547-62 (Sep 1997) ISSN: 0385-0684 [Print] Japan
• PMID: 9309154 (Publication Type: English Abstract, Journal Article, Review)

Chemical References

• Antineoplastic Agents
• Dipeptides
• Enzyme Inhibitors
• Protease Inhibitors
• Succinates
• L-N-(N-hydroxy-2-isobutylsuccinamoyl)seryl-L-valine
• Doxorubicin
• butyrolactone I
• Cyclin-Dependent Kinases
• Metalloendopeptidases
• 4-Butyrolactone

Topics

• 4-Butyrolactone (analogs & derivatives, pharmacology)
• Animals
• Antineoplastic Agents (pharmacology)
• Colonic Neoplasms (pathology)
• Cyclin-Dependent Kinases (antagonists & inhibitors)
• Dipeptides (pharmacology)
• Doxorubicin (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Fibrosarcoma (pathology)
• Humans
• Metalloendopeptidases (antagonists & inhibitors)
• Mice
• Mice, Nude
• Protease Inhibitors (pharmacology)
• Succinates (pharmacology)