13434-13-4

13434-13-4 structure

Name: ACTINONIN
Chemical Name: actinonin
CAS Number: 13434-13-4
Molecular Formula: C₁₉H₃₅N₃O₅
Molecular Weight: 385.498
Catalog: Signaling Pathways Anti-infection Bacterial
Create Date: 2018-09-26 11:11:59
Modify Date: 2024-01-13 16:48:09
Actinonin ((-)-Actinonin) is a naturally occurring antibacterial agent produced by Actinomyces. Actinonin inhibits aminopeptidase M, aminopeptidase N and leucine aminopeptidase. Actinonin is a potent reversible peptide deformylase (PDF) inhibitor with a Ki of 0.28 nM. Actinonin also inhibits MMP-1, MMP-3, MMP-8, MMP-9, and hmeprin α with Ki values of 300 nM, 1,700 nM, 190 nM, 330 nM, and 20 nM, respectively. Actinonin is an apoptosis inducer. Actinonin has antiproliferative and antitumor activities[1][2][3][4][5].

Name	actinonin
Synonyms	Butanediamide, N-hydroxy-N-[(1S)-1-[[(2S)-2-(hydroxymethyl)-1-pyrrolidinyl]carbonyl]-2-methylpropyl]-2-pentyl-, (2R)- Actinonine MFCD00080257 hylpropyl)carbamoyl) (2R)-N-Hydroxy-N-{(2S)-1-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl}-2-pentylsuccinamide (2R)-N-Hydroxy-N-{(2S)-1-[(2S)-2-(hydroxymethyl)-1-pyrrolidinyl]-3-methyl-1-oxo-2-butanyl}-2-pentylsuccinamide

Description	Actinonin ((-)-Actinonin) is a naturally occurring antibacterial agent produced by Actinomyces. Actinonin inhibits aminopeptidase M, aminopeptidase N and leucine aminopeptidase. Actinonin is a potent reversible peptide deformylase (PDF) inhibitor with a Ki of 0.28 nM. Actinonin also inhibits MMP-1, MMP-3, MMP-8, MMP-9, and hmeprin α with Ki values of 300 nM, 1,700 nM, 190 nM, 330 nM, and 20 nM, respectively. Actinonin is an apoptosis inducer. Actinonin has antiproliferative and antitumor activities[1][2][3][4][5].
Related Catalog	Signaling Pathways >> Apoptosis >> Apoptosis Research Areas >> Cancer Research Areas >> Infection Signaling Pathways >> Metabolic Enzyme/Protease >> Aminopeptidase Signaling Pathways >> Metabolic Enzyme/Protease >> MMP Signaling Pathways >> Anti-infection >> Bacterial
Target	Ki: 0.28 nM (Peptide deformylase (PDF))[2], 300 nM (MMP-1), 1,700 nM (MMP-3), 190 nM (MMP-8), 330 nM (MMP-9)[3], and 20 nM (hmeprin α)[5] Apoptosis[1] Aminopeptidase M, Aminopeptidase N and Leucine aminopeptidase[1]
In Vitro	Actinonin inhibits cell growth in various human tumor cell lines. The IC50 of 4, 6.9, 12.8, 16.6, 27.4, 15.7 and 49.3 μM for Raji cells, MDA-MB-468 cells,PC3 cells, SK-LC-19 cells, Hela cells, HT-1080 cells and AL67 cells, respectively[1]. HsPDF is a critical target of actinonin and that the inhibition of this protein in the mitochondria leads to cell death in tumor cells. Actinonin treatment of cells led to a tumor-specific mitochondrial membrane depolarization and ATP depletion in a time- and dose-dependent manner[1]. Actinonin is a potent inhibitor of all three forms (Zn-, Ni-, and Fe-) of peptide deformylases from both S. aureus and E. coli bacteria. Under the assay conditions, the IC50 values for Actinonin are 90, 3, 0.8, and 11 nM for Zn-PDF (E. coli), Ni-PDF (E. coli), Fe-PDF (E. coli), and Ni-PDF (S. aureus), respectively[2]. Actinonin is active against Gram-positive bacteria, including S. aureus (MIC value of 8-16 µg/mL), Streptococcus pyogenes (MIC value of 8 µg/mL) and Streptococcus epidermidis (MIC value of 2-4 µg/mL). Actinonin is also active against fastidious Gramne-gative bacteria, such as H. influenzae (MIC value of 1-2 µg/mL), Moraxella catarrhalis (MIC value of 0.5 µg/mL), and Neisseria gonorrheae (MIC value of 1-4 µg/mL). Actinonin is very active against the H. influenzae acr (MIC value of 0.13 µg/mL) and E. coli acr (MIC value of 0.25 µg/mL) efflux pump mutants[2].
In Vivo	Actinonin has been safely administered to mice as an antibiotic at doses up to 400 mg/kg. Actinonin does not appear to have significant toxicity to normal tissues, despite its antitumor activity in vitro. Remarkably, Actinonin exhibits significant antitumor activity when given i.p. or orally in a CWR22 human prostate tumor xenograft model in nude mice. During treatment, the animals show no signs of toxicity[1].
References	[1]. Lee MD, et al. Human mitochondrial peptide deformylase, a new anticancer target of actinonin-based antibiotics. J Clin Invest. 2004 Oct;114(8):1107-16. [2]. Chen DZ, et al. Actinonin, a naturally occurring antibacterial agent, is a potent deformylase inhibitor. Biochemistry. 2000 Feb 15;39(6):1256-62. [3]. Wahl, R.C., et al. Hydroxamate inhibitors of human gelatinase B (92 kDa). Bioorganic & Medicinal Chemistry Letters 5(4), 349-352 (1995). [4]. Duke SO, et al. Modes of action of microbially-produced phytotoxins. Toxins (Basel). 2011 Aug;3(8):1038-64. [5]. Kruse MN, et al. Human meprin alpha and beta homo-oligomers: cleavage of basement membrane proteins and sensitivity to metalloprotease inhibitors. Biochem J. 2004 Mar 1;378(Pt 2):383-9.

Density	1.1±0.1 g/cm3
Melting Point	137-139ºC
Molecular Formula	C₁₉H₃₅N₃O₅
Molecular Weight	385.498
Exact Mass	385.257660
PSA	118.97000
LogP	0.59
Index of Refraction	1.513
Storage condition	−20°C

CHEMICAL IDENTIFICATION

RTECS NUMBER :: RG9900700

CHEMICAL NAME :: Octanohydroxamic acid, 3-((1-((2-(hydroxymethyl)-1-pyrrolidinyl)carbonyl)-2- methylpropyl) carbamoyl)-

CAS REGISTRY NUMBER :: 13434-13-4

LAST UPDATED :: 199512

DATA ITEMS CITED :: 3

MOLECULAR FORMULA :: C19-H35-N3-O5

MOLECULAR WEIGHT :: 385.57

WISWESSER LINE NOTATION :: T5NTJ AVYY1&1&MVY5&1VMQ B1Q

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >250 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JANTAJ Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo, 141, Japan) V.2-5, 1948-52; V.21- 1968- Volume(issue)/page/year: 38,1629,1985

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 400 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: 85FZAT "Index of Antibiotics from Actinomycetes," Umezawa, H. et al., eds., Tokyo, Univ. of Tokyo Press, 1967 Volume(issue)/page/year: -,102,1967

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >400 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #167936

Personal Protective Equipment	Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter
Safety Phrases	S22-S24/25
RIDADR	NONH for all modes of transport
WGK Germany	3
RTECS	RG9900700

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