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| 1mg |
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| Targets |
The primary targets of Destruxin B are the components of the mitochondrial apoptotic pathway. It induces apoptosis via a Bcl-2 family-dependent mitochondrial pathway. This involves the activation of pro-apoptotic Bcl-2 family members, leading to mitochondrial outer membrane permeabilization, release of cytochrome c, and activation of caspase-3. Destruxin B also modulates the Wnt/beta-catenin signaling pathway in hepatocellular carcinoma cells. In insects, Destruxin B disrupts cellular processes by inhibiting the immune response. The compound's ability to target multiple pathways contributes to its insecticidal and anticancer activities.
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| ln Vitro |
Destruxin B (1-30 μM; 48 hours) suppresses H1299 and A549 cells' ability to proliferate, with IC50 values of 4.1 μM and 4.9 μM, respectively [1]. The apoptosis inducible by Destruxin B (1-30 μM; 48 hours) in A549 cells is largely due to the activation of the mitochondria-dependent caspase cascade [1]. In a time- and dose-dependent manner, destruxin B (1.25-20.00 μM; 72 hours) therapy dramatically reduced the viability of HT-29 human colorectal cancer cells [2]. A549 cells treated with destruxin B (10 or 20 μM; 12 and 24 hours) showed a concentration- and time-dependent increase in the pro-apoptotic protein PUMA and a decrease in the anti-apoptotic protein Mcl-1 [1].
In vitro, Destruxin B has been shown to induce apoptosis in various cancer cell lines. It induces apoptosis in human non-small cell lung cancer cells (H1299 and A549) through a Bcl-2 family-dependent mitochondrial pathway. It selectively inhibits the growth of human oral cancer cell lines. Destruxin B also inhibits the growth of hepatocellular carcinoma cells by modulating the Wnt/beta-catenin pathway. The compound significantly activates caspase-3 and reduces tumor cell proliferation through caspase-mediated apoptosis. Its cytotoxic effects are dose- and time-dependent, with concentrations ranging from 1-30 microM used in various studies. |
| ln Vivo |
In a dose- and time-dependent way, Destruxin B (DB) (injection; 0.6–15 mg/kg/day for 6 weeks) inhibits the growth of tumors [2].
In vivo, Destruxin B has demonstrated anticancer activity in animal models. It significantly activates caspase-3 and reduces tumor cell proliferation through caspase-mediated apoptosis in vivo. In a dose- and time-dependent manner, Destruxin B (injection; 0.6-15 mg/kg/day for 6 weeks) inhibits tumor growth. The compound has been shown to reduce tumor growth in xenograft models of non-small cell lung cancer and other tumor types. Its insecticidal activity has also been demonstrated in vivo, where it effectively targets pests without harming humans or animals. Destruxin B's in vivo efficacy supports its potential as an anticancer agent and a biocontrol agent. |
| Enzyme Assay |
The in vitro enzyme activity of Destruxin B can be assessed using cell-free assays for caspase activity. A typical protocol involves preparing cell lysates from treated cells and incubating them with a fluorogenic caspase-3 substrate (e.g., Ac-DEVD-AMC) in a reaction buffer. The release of fluorescent AMC is measured over time using a fluorescence plate reader. The level of caspase-3 activation is expressed as fold-increase over untreated controls. For studies on mitochondrial membrane potential, isolated mitochondria are incubated with Destruxin B, and the membrane potential is measured using a fluorescent probe such as JC-1 or TMRM.
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| Cell Assay |
Cell proliferation experiment [1]
Cell Types: H1299 cells Tested Concentrations: 1, 5, 10, 20, 30 μM Incubation Duration: 48 hrs (hours) Experimental Results: Inhibits H1299 cell proliferation, IC50 is 4.1 μM. Apoptosis analysis [1] Cell Types: Lung adenocarcinoma A549 cells Tested Concentrations: 1,5,10,20,30 μM Incubation Duration: 48 hrs (hours) Experimental Results: Induced caspase-dependent lung adenocarcinoma A549 cell death. Cell viability assay [2] Cell Types: HT-29 human colorectal cancer cells Tested Concentrations: 1.25, 2.50, 5.00, 10.00 and 20.00 μM Incubation Duration: 72 hrs (hours) Experimental Results: The IC50 measured at 24 hrs (hours), 48 hrs (hours) and 72 hrs (hours) was 14.97, 2.00 and 0.67 μM respectively. Western Blot Analysis[1] Cell Types: A549 Cell Tested Concentrations: 10 or 20 μM Incubation Duration: 12 and 24 hrs (hours) Experimental Results: Regulation of Mcl-1 and PUMA. For in vitro cellular experiments, cancer cell lines (e.g., A549, H1299, HT-29) are cultured in appropriate media and treated with Destruxin B at various concentrations (typically 1-30 microM) for 24-72 hours. Cell viability is measured using MTT, CCK-8, or other cell proliferation assays. Apoptosis is assessed by flow cytometry using Annexin V/PI staining or by measuring caspase-3/7 activity using a luminescent assay. Mitochondrial membrane potential is measured using fluorescent probes such as JC-1. Protein expression (e.g., Bcl-2, Bax, cytochrome c, caspase-3) is assessed by Western blot. The duration of treatment and concentration of the compound can be optimized depending on the cell type and experimental objectives. |
| Animal Protocol |
Animal/Disease Models: Athymic female nude mice (BALB/cAnN.Cg-Foxn1nu/CrlNarl), approximately 4-5 weeks old on arrival [2]
Doses: low dose (0.6 mg/kg), medium dose (3 mg/kg) , High dose (15 mg/kg) Route of Administration: injection; daily; lasted for 6 weeks. Experimental Results: Low dose, medium dose and high dose demonstrated a reduction of 23.9%, 33.4% and 55.8% in average tumor size, respectively. In vivo animal experiments with Destruxin B typically involve injection administration in mice. A common dosing regimen is 0.6-15 mg/kg/day for 6 weeks. For xenograft studies, tumor-bearing mice are treated with Destruxin B via intravenous or intraperitoneal injection, and tumor growth is monitored by caliper measurements. The compound's effect on apoptosis is assessed by immunohistochemical staining for cleaved caspase-3 or TUNEL staining in tumor tissues. For insecticidal studies, Destruxin B is applied to insects (e.g., Spodoptera exigua) at various concentrations, and mortality is recorded over time. Blood and tissue samples are collected for biochemical analysis. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for Destruxin B are limited. The compound has been shown to have pharmacokinetic properties similar to those found in vivo. It is soluble in organic solvents such as DMSO and dichloromethane. Destruxin B is typically administered by injection in animal studies. Its absorption, distribution, metabolism, and excretion properties would need to be further characterized to support its development as a therapeutic agent. The compound's lipophilic nature and cyclic depsipeptide structure may influence its pharmacokinetic profile.
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| Toxicity/Toxicokinetics |
The toxicity profile of Destruxin B has not been extensively characterized. In insects, Destruxin B is toxic and acts as an insecticide. In mammalian systems, the compound has shown anticancer activity with selectivity for cancer cells over normal cells. However, its potential toxicity to normal tissues has not been fully evaluated. In animal studies, Destruxin B has been administered at doses up to 15 mg/kg/day for 6 weeks without significant adverse effects reported. Further toxicological studies are needed to assess its safety profile for potential therapeutic use. The compound should be handled with standard laboratory precautions.
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| References |
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| Additional Infomation |
Unii-7R6CR62kfe has been reported in Metarhizium anisopliae, Metarhizium septemlobus, and Alternaria lobata, and available data are available.
Destruxin B is a cyclic depsipeptide isolated from the entomopathogenic fungus Metarhizium anisopliae. It exhibits insecticidal and anticancer activities. Destruxin B induces apoptosis in human non-small cell lung cancer cells through a Bcl-2 family-dependent mitochondrial pathway. It significantly activates caspase-3 and reduces tumor cell proliferation through caspase-mediated apoptosis in vitro and in vivo. The compound also inhibits hepatocellular carcinoma cell growth via modulation of the Wnt/beta-catenin pathway. Destruxin B has potential applications in agriculture as a biocontrol agent and in cancer therapy. It is available as a research compound and is not approved for clinical use. |
| Molecular Formula |
C30H51N5O7
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|---|---|
| Molecular Weight |
593.75524
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| Exact Mass |
593.379
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| CAS # |
2503-26-6
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| PubChem CID |
11124817
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| Appearance |
White to off-white solid powder
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| Density |
1.17g/cm3
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| Boiling Point |
875ºC at 760mmHg
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| Flash Point |
483ºC
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| Vapour Pressure |
4.15E-31mmHg at 25°C
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| Index of Refraction |
1.535
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| LogP |
1.787
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
42
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| Complexity |
1020
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| Defined Atom Stereocenter Count |
6
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| SMILES |
CC[C@H](C)[C@H]1C(=O)N([C@H](C(=O)N([C@H](C(=O)NCCC(=O)O[C@@H](C(=O)N2CCC[C@H]2C(=O)N1)CC(C)C)C)C)C(C)C)C
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| InChi Key |
GNBHVMBELHWUIF-VTSYCQLTSA-N
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| InChi Code |
InChI=1S/C30H51N5O7/c1-10-19(6)24-29(40)34(9)25(18(4)5)30(41)33(8)20(7)26(37)31-14-13-23(36)42-22(16-17(2)3)28(39)35-15-11-12-21(35)27(38)32-24/h17-22,24-25H,10-16H2,1-9H3,(H,31,37)(H,32,38)/t19-,20-,21-,22+,24-,25-/m0/s1
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| Chemical Name |
(3R,10S,13S,16S,19S)-16-[(2S)-butan-2-yl]-10,11,14-trimethyl-3-(2-methylpropyl)-13-propan-2-yl-4-oxa-1,8,11,14,17-pentazabicyclo[17.3.0]docosane-2,5,9,12,15,18-hexone
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6842 mL | 8.4209 mL | 16.8418 mL | |
| 5 mM | 0.3368 mL | 1.6842 mL | 3.3684 mL | |
| 10 mM | 0.1684 mL | 0.8421 mL | 1.6842 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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