Actinonin
Actinonin is a naturally occurring antibacterial agent that has demonstrated anti-tumor activity. Actinonin is also an antibiotic and CD13/aminopeptidase N (APN) inhibitor, has been shown to be cytotoxic to tumor cell lines in vitro. Actinonin inhibited growth of NB4 and HL60 human cell lines and AKR mouse leukemia cells in vitro with an IC50 of about 2-5 micrograms/ml. Actinonin induces a G1 arrest in HL60 and NB4 cells; apoptosis was observed in 20-35% of the cells. Actinonin showed dose-dependent antitumor effects on AKR leukemia in vivo, resulting in a survival advantage.
1: Fernández-San Millán A, Obregón P, Veramendi J. Over-expression of peptide deformylase in chloroplasts confers actinonin resistance, but is not a suitable selective marker system for plastid transformation. Transgenic Res. 2011 Jun;20(3):613-24. doi: 10.1007/s11248-010-9447-9. Epub 2010 Oct 9. PubMed PMID: 20936344.
2: Wang Z, Herzog C, Kaushal GP, Gokden N, Mayeux PR. Actinonin, a meprin A inhibitor, protects the renal microcirculation during sepsis. Shock. 2011 Feb;35(2):141-7. doi: 10.1097/SHK.0b013e3181ec39cc. PubMed PMID: 20577148; PubMed Central PMCID: PMC3265793.
3: Larue V, Seijo B, Tisne C, Dardel F. 1H, 13C and 15N NMR assignments of the E. coli peptide deformylase in complex with a natural inhibitor called actinonin. Biomol NMR Assign. 2009 Jun;3(1):153-5. doi: 10.1007/s12104-009-9164-6. Epub 2009 May 7. PubMed PMID: 19636969.
4: Sina A, Lord-Dufour S, Annabi B. Cell-based evidence for aminopeptidase N/CD13 inhibitor actinonin targeting of MT1-MMP-mediated proMMP-2 activation. Cancer Lett. 2009 Jul 8;279(2):171-6. doi: 10.1016/j.canlet.2009.01.032. Epub 2009 Mar 4. PubMed PMID: 19264392.
5: Berg AK, Srivastava DK. Delineation of alternative conformational states in Escherichia coli peptide deformylase via thermodynamic studies for the binding of actinonin. Biochemistry. 2009 Feb 24;48(7):1584-94. doi: 10.1021/bi8019542. PubMed PMID: 19191548; PubMed Central PMCID: PMC2644421.
6: Zhang D, Wang Z, Xu W, Sun F, Tang L, Wang J. Design, synthesis and antibacterial activity of novel actinonin derivatives containing benzimidazole heterocycles. Eur J Med Chem. 2009 May;44(5):2202-10. doi: 10.1016/j.ejmech.2008.05.009. Epub 2008 May 23. PubMed PMID: 18617291.
7: Sato S, Tetsuhashi M, Sekine K, Miyachi H, Naito M, Hashimoto Y, Aoyama H. Degradation-promoters of cellular inhibitor of apoptosis protein 1 based on bestatin and actinonin. Bioorg Med Chem. 2008 Apr 15;16(8):4685-98. doi: 10.1016/j.bmc.2008.02.024. Epub 2008 Feb 13. PubMed PMID: 18313309.
8: Takayama J, Takaoka M, Yamamoto S, Nohara A, Ohkita M, Matsumura Y. Actinonin, a meprin inhibitor, protects ischemic acute kidney injury in male but not in female rats. Eur J Pharmacol. 2008 Feb 26;581(1-2):157-63. Epub 2007 Nov 28. PubMed PMID: 18093581.
9: Park JK, Moon JH, Kim JH, Kim EE. Crystallization and preliminary X-ray crystallographic analysis of peptide deformylase (PDF) from Bacillus cereus in ligand-free and actinonin-bound forms. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Jan 1;61(Pt 1):150-2. Epub 2004 Dec 24. PubMed PMID: 16508119; PubMed Central PMCID: PMC1952381.
10: Grujic M, Zavasnik-Bergant T, Pejler G, Renko M. Actinonin induces apoptosis in U937 leukemia cells. Cancer Lett. 2005 Jun 8;223(2):211-8. Epub 2004 Dec 13. PubMed PMID: 15896455.
2: Wang Z, Herzog C, Kaushal GP, Gokden N, Mayeux PR. Actinonin, a meprin A inhibitor, protects the renal microcirculation during sepsis. Shock. 2011 Feb;35(2):141-7. doi: 10.1097/SHK.0b013e3181ec39cc. PubMed PMID: 20577148; PubMed Central PMCID: PMC3265793.
3: Larue V, Seijo B, Tisne C, Dardel F. 1H, 13C and 15N NMR assignments of the E. coli peptide deformylase in complex with a natural inhibitor called actinonin. Biomol NMR Assign. 2009 Jun;3(1):153-5. doi: 10.1007/s12104-009-9164-6. Epub 2009 May 7. PubMed PMID: 19636969.
4: Sina A, Lord-Dufour S, Annabi B. Cell-based evidence for aminopeptidase N/CD13 inhibitor actinonin targeting of MT1-MMP-mediated proMMP-2 activation. Cancer Lett. 2009 Jul 8;279(2):171-6. doi: 10.1016/j.canlet.2009.01.032. Epub 2009 Mar 4. PubMed PMID: 19264392.
5: Berg AK, Srivastava DK. Delineation of alternative conformational states in Escherichia coli peptide deformylase via thermodynamic studies for the binding of actinonin. Biochemistry. 2009 Feb 24;48(7):1584-94. doi: 10.1021/bi8019542. PubMed PMID: 19191548; PubMed Central PMCID: PMC2644421.
6: Zhang D, Wang Z, Xu W, Sun F, Tang L, Wang J. Design, synthesis and antibacterial activity of novel actinonin derivatives containing benzimidazole heterocycles. Eur J Med Chem. 2009 May;44(5):2202-10. doi: 10.1016/j.ejmech.2008.05.009. Epub 2008 May 23. PubMed PMID: 18617291.
7: Sato S, Tetsuhashi M, Sekine K, Miyachi H, Naito M, Hashimoto Y, Aoyama H. Degradation-promoters of cellular inhibitor of apoptosis protein 1 based on bestatin and actinonin. Bioorg Med Chem. 2008 Apr 15;16(8):4685-98. doi: 10.1016/j.bmc.2008.02.024. Epub 2008 Feb 13. PubMed PMID: 18313309.
8: Takayama J, Takaoka M, Yamamoto S, Nohara A, Ohkita M, Matsumura Y. Actinonin, a meprin inhibitor, protects ischemic acute kidney injury in male but not in female rats. Eur J Pharmacol. 2008 Feb 26;581(1-2):157-63. Epub 2007 Nov 28. PubMed PMID: 18093581.
9: Park JK, Moon JH, Kim JH, Kim EE. Crystallization and preliminary X-ray crystallographic analysis of peptide deformylase (PDF) from Bacillus cereus in ligand-free and actinonin-bound forms. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Jan 1;61(Pt 1):150-2. Epub 2004 Dec 24. PubMed PMID: 16508119; PubMed Central PMCID: PMC1952381.
10: Grujic M, Zavasnik-Bergant T, Pejler G, Renko M. Actinonin induces apoptosis in U937 leukemia cells. Cancer Lett. 2005 Jun 8;223(2):211-8. Epub 2004 Dec 13. PubMed PMID: 15896455.
| Chemical | |
|---|---|
| CAS Num | 13434-13-4 |
| Chemical Formula | C19H35N3O5 |
| Molecular Weight | 385.5 |
| IUPAC Chemical Name | (R)-N4-hydroxy-N1-((S)-1-((S)-2-(hydroxymethyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)-2-pentylsuccinamide |
| Exact Mass | 385.25767 |
| Elemental Analysis | C, 59.20; H, 9.15; N, 10.90; O, 20.75 |
| Synonym | Actinonin. |
| Solubility | Soluble in DMSO, not in water |
| SMILES Code | O=C(N[C@@H](C(C)C)C(N1[C@H](CO)CCC1)=O)[C@H](CCCCC)CC(NO)=O |
| Biological | |
| Targets and Effects | CD13/aminopeptidase N (APN) inhibitor |
| Pathways | Apoptosis |
| Physical | |
| Appearance | Solid powder |
| Purity | >98% (or refer to the Certificate of Analysis) |
| Shipping Condition | Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs. |
| Storage Condition | Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years). |
| Shelf Life | >5 years if stored properly |
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