Actinonin (Synonyms: (-)-Actinonin,Ro 06-1467) |
Catalog No.GC16350
One-Click Copy Product Info
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Actinonin, a peptidomimetic antibiotic that inhibits enkephalin-aminopeptidase, enkephalinase A, and dipeptidylaminopeptidase with IC50 values of 0.39μM, 5.6μM, and 1.1μM, respectively.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 13434-13-4
Sample solution is provided at 25 µL, 10mM.
Actinonin, a peptidomimetic antibiotic that inhibits enkephalin-aminopeptidase, enkephalinase A, and dipeptidylaminopeptidase with IC50 values of 0.39μM, 5.6μM, and 1.1μM, respectively[1]. Actinonin can inhibit the constitutive expression of functional recombinant MT1-MMP protein, block the activation of proMMP-2, and suppress angiogenesis[2]. Actinonin has been widely used as an antibacterial agent to inhibit the growth of Gram-positive bacteria and difficult-to-culture Gram-negative bacteria[3].
In vitro, Actinonin treatment for 5 days significantly inhibited the viability of HL-60 cells, NB4 cells and AKR cells with IC50 values of 2µg/ml, 5µg/ml, and 3µg/ml, respectively[4]. Treatment of U937 cells with 20μg/ml of Actinonin for 24 hours significantly induced cell apoptosis, accompanied by a significant increase in the activities of caspase-3 and caspase-7-like enzymes and extensive fragmentation of DNA[5]. Actinonin pretreatment at 26nM for 1 hour can reduce the expression of HSP70 induced by celastrol in U937 cells, and synergistically inhibit cell proliferation with celastrol[6].
In vivo, Actinonin treatment via daily intraperitoneal injection (150mg/kg/day) for 2 weeks significantly inhibited tumor growth in the A549 xenograft mouse model without causing any toxic reactions[7]. Thirty minutes before the mice underwent cecal ligation and puncture (CLP), a single dose of Actinonin (20mg/kg) was injected intraperitoneally, which could reduce the serum IL-1β level and prevent the decline in renal capillary perfusion[8].
References:
[1] Hachisu M, Hiranuma T, Murata S, et al. Analgesic effect of actinonin, a new potent inhibitor of multiple enkephalin degrading enzymes[J]. Life sciences, 1987, 41(2): 235-240.
[2] Sina A, Lord-Dufour S, Annabi B. Cell-based evidence for aminopeptidase N/CD13 inhibitor actinonin targeting of MT1-MMP-mediated proMMP-2 activation[J]. Cancer letters, 2009, 279(2): 171-176.
[3] Chen D Z, Patel D V, Hackbarth C J, et al. Actinonin, a naturally occurring antibacterial agent, is a potent deformylase inhibitor[J]. Biochemistry, 2000, 39(6): 1256-1262.
[4] Xu Y, Lai L T, Gabrilove J L, et al. Antitumor activity of actinonin in vitro and in vivo[J]. Clinical cancer research: an official journal of the American Association for Cancer Research, 1998, 4(1): 171-176.
[5] Grujic M, Zavasnik-Bergant T, Pejler G, et al. Actinonin induces apoptosis in U937 leukemia cells[J]. Cancer letters, 2005, 223(2): 211-218.
[6] Peng B, Zhang X, Cao F, et al. Peptide deformylase inhibitor actinonin reduces celastrol’s HSP70 induction while synergizing proliferation inhibition in tumor cells[J]. Bmc Cancer, 2014, 14(1): 146.
[7] Lee M D, She Y, Soskis M J, et al. Human mitochondrial peptide deformylase, a new anticancer target of actinonin-based antibiotics[J]. The Journal of clinical investigation, 2004, 114(8): 1107-1116.
[8] Wang Z, Herzog C, Kaushal G P, et al. Actinonin, a meprin A inhibitor, protects the renal microcirculation during sepsis[J]. Shock, 2011, 35(2): 141-147.
| Cell experiment [1]: | |
Cell lines | U937 cells |
Preparation Method | The U937 cells were suspended in RPMI 1640 medium containing 10% fetal bovine serum (FBS) and 2mM glutamine at a final concentration of 1.5×105 cells/ml, and then inoculated into 24-well culture plates. Subsequently, different concentrations of Actinonin (2.5, 5, 10, and 20μg/ml) were added to each well, and the culture plates were placed in a humidified incubator at 37°C and 5% CO2 for 72h. The cells were counted every day and stained with trypan blue. |
Reaction Conditions | 2.5, 5, 10, and 20μg/ml; 72h |
Applications | Actinonin treatment inhibited the proliferation and viability of U937 cells in a concentration-dependent manner. |
| Animal experiment [2]: | |
Animal models | Athymic NCr-nu mice |
Preparation Method | Subcutaneously inoculate A549 cells (5×106) on the lateral abdomen of 8 to 10-week-old athymic NCr-nu mice. Once the tumors can be felt, the mice were randomly divided into a control group and a treatment group, with 3-5 mice in each group. The control group was given a vehicle intraperitoneally and the treatment group was intraperitoneal injection of 150mg/kg of Actinonin, once a day, for 2 weeks. The tumor size was measured with a vernier caliper every 3-4 days. |
Dosage form | 150mg/kg/day for 2 weeks; i.p. |
Applications | Actinonin treatment significantly reduced tumor growth in the A549 cell-xenograft mouse model. |
References: | |
| Cas No. | 13434-13-4 | SDF | |
| Synonyms | (-)-Actinonin,Ro 06-1467 | ||
| Chemical Name | (2R)-N4-hydroxy-N1-[(1S)-1-[[(2S)-2-(hydroxymethyl)-1-pyrrolidinyl]carbonyl]-2-methylpropyl]-2-pentyl-butanediamide | ||
| Canonical SMILES | O=C([C@H](C(C)C)NC([C@H](CCCCC)CC(NO)=O)=O)N1CCC[C@H]1CO | ||
| Formula | C19H35N3O5 | M.Wt | 385.5 |
| Solubility | 30mg/ml in ethanol;30mg/ml in DMSO;30mg/ml in dimethyl formamide | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.594 mL | 12.9702 mL | 25.9403 mL |
| 5 mM | 518.8 μL | 2.594 mL | 5.1881 mL |
| 10 mM | 259.4 μL | 1.297 mL | 2.594 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 22 reference(s) in Google Scholar.)