(-)-Actinonin

• CAT Number: R000760
• CAS Number: 13434-13-4
• Molecular Formula: C19H35N3O5
• Molecular Weight: 385.5
• Purity: ≥95%
• Storage: -20°C
• InChI: InChI=1S/C19H35N3O5/c1-4-5-6-8-14(11-16(24)21-27)18(25)20-17(13(2)3)19(26)22-10-7-9-15(22)12-23/h13-15,17,23,27H,4-12H2,1-3H3,(H,20,25)(H,21,24)/t14-,15+,17+/m1/s1
• InChIKey: XJLATMLVMSFZBN-VYDXJSESSA-N
• SMILES: O=C([C@H](C(C)C)NC([C@H](CCCCC)CC(NO)=O)=O)N1CCC[C@H]1CO

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.

Reference

1:The Inhibition and Resistance Mechanisms of Actinonin, Isolated from Marine Streptomyces sp. NHF165, against Vibrio anguillarum. Yang N, Sun C.Front Microbiol. 2016 Sep 13;7:1467. doi: 10.3389/fmicb.2016.01467. eCollection 2016. PMID: 27679625 Free PMC Article2:Crystal Structures of Peptide Deformylase from Rice Pathogen Xanthomonas oryzae pv. oryzae in Complex with Substrate Peptides, Actinonin, and Fragment Chemical Compounds. Ngo HP, Ho TH, Lee I, Tran HT, Sur B, Kim S, Kim JG, Ahn YJ, Cha SS, Kang LW.J Agric Food Chem. 2016 Oct 5;64(39):7307-7314. Epub 2016 Sep 21. PMID: 27616570 3:Structural basis for the inhibition of M1 family aminopeptidases by the natural product actinonin: Crystal structure in complex with E. coli aminopeptidase N. Ganji RJ, Reddi R, Gumpena R, Marapaka AK, Arya T, Sankoju P, Bhukya S, Addlagatta A.Protein Sci. 2015 May;24(5):823-31. doi: 10.1002/pro.2653. Epub 2015 Apr 8. PMID: 25644575 Free PMC Article4:Peptide deformylase inhibitor actinonin reduces celastrol/’s HSP70 induction while synergizing proliferation inhibition in tumor cells. Peng B, Zhang X, Cao F, Wang Y, Xu L, Cao L, Yang C, Li M, Uzan G, Zhang D.BMC Cancer. 2014 Mar 4;14:146. doi: 10.1186/1471-2407-14-146. PMID: 24589236 Free PMC Article5:Over-expression of peptide deformylase in chloroplasts confers actinonin resistance, but is not a suitable selective marker system for plastid transformation. Fernández-San Millán A, Obregón P, Veramendi J.Transgenic Res. 2011 Jun;20(3):613-24. doi: 10.1007/s11248-010-9447-9. Epub 2010 Oct 9. PMID: 20936344 6:Actinonin, a meprin A inhibitor, protects the renal microcirculation during sepsis. Wang Z, Herzog C, Kaushal GP, Gokden N, Mayeux PR.Shock. 2011 Feb;35(2):141-7. doi: 10.1097/SHK.0b013e3181ec39cc. PMID: 20577148 Free PMC Article7:1H, 13C and 15N NMR assignments of the E. coli peptide deformylase in complex with a natural inhibitor called actinonin. Larue V, Seijo B, Tisne C, Dardel F.Biomol NMR Assign. 2009 Jun;3(1):153-5. doi: 10.1007/s12104-009-9164-6. Epub 2009 May 7. PMID: 19636969 8:Cell-based evidence for aminopeptidase N/CD13 inhibitor actinonin targeting of MT1-MMP-mediated proMMP-2 activation. Sina A, Lord-Dufour S, Annabi B.Cancer Lett. 2009 Jul 8;279(2):171-6. doi: 10.1016/j.canlet.2009.01.032. Epub 2009 Mar 4. PMID: 19264392 9:Delineation of alternative conformational states in Escherichia coli peptide deformylase via thermodynamic studies for the binding of actinonin. Berg AK, Srivastava DK.Biochemistry. 2009 Feb 24;48(7):1584-94. doi: 10.1021/bi8019542. PMID: 19191548 Free PMC Article10:Design, synthesis and antibacterial activity of novel actinonin derivatives containing benzimidazole heterocycles. Zhang D, Wang Z, Xu W, Sun F, Tang L, Wang J.Eur J Med Chem. 2009 May;44(5):2202-10. doi: 10.1016/j.ejmech.2008.05.009. Epub 2008 May 23. PMID: 18617291