Murabutide
Murabutide is an immunomodulator and also a NOD2 receptor agonist. Murabutide enhances the signal transduction of ATR and NOD2, mediates the activation of the DDR pathway, and thereby repairs radiation-induced DNA double-strand breaks. Murabutide inhibits radiation-induced cell apoptosis and protects cells and mice from radiation-induced toxic damage. Murabutide induces the expression and DNA-binding activity of Oct-1 in macrophages, thereby inhibiting the transcription and replication of HIV-1. Murabutide reduces the expression levels of CD4 and CCR5 on the surface of macrophages, and induces the secretion of β-chemokines, TNF-α and IL-6. Murabutide enhances non-specific viral resistance and targets reticuloendothelial cells. Murabutide can be used in research related to radiation-induced damage and human immunodeficiency virus type 1 infection.
For research use only. We do not sell to patients.
- CAS No.: 74817-61-1
- Formula: C23H40N4O11
- Molecular Weight:548.58
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
In Vitro
Murabutide (0.25-5 μg/mL; 2 h pretreatment prior to 8 Gy IR, measured 24 h post-IR) significantly increases the survival rate of HIEC cells at 24 h post-irradiation, with the strongest effect observed at the concentration of 1 μg/mL[1].
Murabutide (1 μg/mL; pretreated for 2 h prior to 10 Gy IR, measured at 24 h post-IR) significantly inhibits apoptosis of HIEC cells at 24 h post-irradiation, and this effect depends on the ATR signaling pathway, as combined treatment with the ATR inhibitor VE-821 (HY-14731) abolishes this effect[1].
Murabutide (1-5 μg/mL; pretreated for 2-12 h prior to 8 Gy IR, harvested 0.5-12 h post-IR) activates NOD2, enhances the phosphorylation levels of key DDR pathway proteins DNAPKcs, ATR and CHK1 in HIEC cells at 0.5 h post-irradiation, upregulates the level of anti-apoptotic protein Bcl2, downregulates the levels of pro-apoptotic protein Bax and activated caspase3, and reduces IR-induced γ-H2AX levels in HIEC cells at 0.5 h and 12 h post-irradiation[1].
Murabutide (1 μg/mL; pretreated 2 h before 8 Gy IR, detected 24 h after IR) exerts DNA damage-protective effects on HIEC cells at 24 h post-irradiation, and this effect depends on the ATR signaling pathway[1].
Murabutide (10 μg/mL; 24 h) significantly regulates the expression of 28 genes in HIV-1-infected MDMs, among which 18 functionally characterized genes are upregulated (including Oct-1, MT-II and IL-13 receptor α-1 chain), and 4 functionally characterized genes are downregulated (including EGR2 and ferritin L chain)[2].
Murabutide (10 μg/mL; 24 h) upregulates the mRNA expression of Oct-1, MT-II and cytochrome b in HIV-1-infected MDM, and downregulates the mRNA expression of EGR2[2].
Murabutide (10 μg/mL; 0-72 h) upregulates the expression of Oct-1 protein in HIV-1-infected MDMs and induces a significant, time-stable increase in Oct-1-specific DNA-binding activity[2].
Murabutide (0.01-100 μg/mL; 6-28 days) potently inhibits the replication of M-tropic, dual-tropic and laboratory-adapted HIV-1 strains in human monocyte-derived macrophages, with an average maximum inhibition rate of 85% at a concentration of 10 μg/mL. This activity persists for at least 28 days without altering cell viability[3].
Murabutide (10 μg/mL; 8 days, 22-48 h) potently reduces HIV-1 mRNA and proviral DNA levels in human monocyte-derived macrophages by inhibiting nuclear transport of the pre-integration complex and proviral DNA integration, without affecting early reverse transcription[3].
Murabutide (0.1-10 μg/mL; ≥8-20 days) inhibits the replication of M-tropic and T-tropic HIV-1 strains in human monocyte-derived dendritic cells; detection at 19 days post-infection shows that the average inhibition rate reaches 77% at the concentration of 10 μg/mL, with no alteration of cell proliferation[3].
Murabutide (10 μg/mL; 6-48 h) significantly reduces the expression of CD4 and CCR5 receptors on the surface of human monocyte-derived macrophages and dendritic cells after 24 h or 48 h of treatment, without altering the expression of CD14, HLA-DR or CXCR4[3].
Murabutide (10 μg/mL; 2-6 days) induces significant secretion of TNF-α, IL-6, and β-chemokines (MIP-1α, MIP-1β, RANTES) in HIV-1-infected human monocyte-derived macrophages and dendritic cells, with persistent induction in MDM and transient induction in MDDC[3].
Murabutide (10 μg/mL; 8-10 days) exhibits HIV-1 inhibitory activity in human monocyte-derived macrophages, and this activity is independent of induced β-chemokine secretion, as neutralization of MIP-1α, MIP-1β and RANTES does not alter its inhibitory effect[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:normal human intestinal epithelial crypt (HIEC) cells
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Concentration:0.25, 0.5, 1, 5 μg/mL
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Incubation Time:2 h pretreatment before 8 Gy IR, measured 24 h post-IR
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Result:Significantly promoted HIEC cell viability after 8 Gy IR, with the most pronounced effect observed at 1 μg/mL; cell viability was significantly higher in all murabutide-treated groups compared to the IR-only group.
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Cell Line:normal human intestinal epithelial crypt (HIEC) cells
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Concentration:1 μg/mL
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Incubation Time:2 h pretreatment before 10 Gy IR, measured 24 h post-IR
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Result:Significantly reduced IR-induced apoptosis in HIEC cells, lowering the apoptosis rate from ~14% in the IR-only group to ~8% in the murabutide-pretreated group.\nSignificantly reduced IR-induced apoptosis in HIEC cells, but this inhibitory effect was eliminated by co-treatment with VE-821, restoring apoptosis rates to levels comparable to the IR-only group.\nSignificantly reduced IR-induced apoptosis in HIEC cells, and co-treatment with KU-55933 did not reverse this anti-apoptotic effect.
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Cell Line:normal human intestinal epithelial crypt (HIEC) cells
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Concentration:1-5 μg/mL
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Incubation Time:2 h pretreatment before 8 Gy IR, harvested 0.5 h post-IR
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Result:Increased the expression of anti-apoptotic Bcl2 and decreased the expression of pro-apoptotic Bax and cleaved caspase3 in HIEC cells after 8 Gy IR, compared to the IR-only group.\nEnhanced NOD2 activation, increased the phosphorylation of DNAPKcs, ATR, and CHK1, and did not alter the phosphorylation of ATM or CHK2 in HIEC cells after 8 Gy IR, compared to the IR-only group.
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Cell Line:normal human intestinal epithelial crypt (HIEC) cells
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Concentration:1 μg/mL
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Incubation Time:2 h or 12 h pretreatment before 8 Gy IR, harvested 0.5 h or 12 h post-IR
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Result:Significantly reduced the IR-induced increase in γ-H2AX levels in HIEC cells at both 0.5 and 12 hours post-irradiation, compared to the IR-only group.
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Cell Line:normal human intestinal epithelial crypt (HIEC) cells
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Concentration:1 μg/mL
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Incubation Time:2 h pretreatment before 8 Gy IR, analyzed 0.5, 8, 12, 24 h post-IR
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Result:Significantly reduced the number of γ-H2AX foci in HIEC cells at all tested time points (0.5, 8, 12, 24 hours) post-8 Gy IR, compared to the IR-only group.
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Cell Line:normal human intestinal epithelial crypt (HIEC) cells
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Concentration:1 μg/mL
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Incubation Time:2 h pretreatment before 8 Gy IR, harvested 0, 0.5, 2, 12 h post-IR
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Result:Increased the phosphorylation of ATR, CHK1, and RPA2 in HIEC cells post-IR, but co-treatment with VE-821 diminished this enhanced phosphorylation, reducing levels to those comparable to the IR-only group.
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Cell Line:normal human intestinal epithelial crypt (HIEC) cells
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Concentration:1 μg/mL
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Incubation Time:2 h pretreatment before 8 Gy IR, analyzed 24 h post-IR
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Result:Significantly reduced the number of γ-H2AX foci in HIEC cells 24 hours post-IR, but co-treatment with VE-821 reversed this effect, increasing foci numbers to levels comparable to the IR-only group.
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Cell Line:HIV-1-infected human monocyte-derived macrophages (MDMs)
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Concentration:10 μg/mL
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Incubation Time:24 h, 48 h, 72 h
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Result:Up-regulated Oct-1 protein levels at 48-hour and 72-hour time points.
Showed no significant change in Oct-1 protein levels at 24-hour time point.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (male, 8-week old)[1]
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Dosage:300 μg/mouse
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Administration:i.p.; single dose (2 hours before irradiation)
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Result:Increased 30-day survival rate to 20% in mice exposed to 8.5 Gy γ-irradiation, compared to 0% in untreated controls.
Increased 30-day survival rate to 50% in mice exposed to 7 Gy γ-irradiation, and extended average survival time compared to untreated controls.
Maintained higher average body weight, better overall health, and prevented diarrhea in mice exposed to 7 Gy γ-irradiation, compared to untreated controls.
Increased the ratio of bone marrow nucleated cells on Day 1 and Day 3 post-7 Gy γ-irradiation, compared to untreated controls.
Increased intestinal villi length and intestinal crypts ratio on Day 1 and Day 3 post-7 Gy γ-irradiation, compared to untreated controls.
Increased white pulp area in the spleen on Day 1 and Day 3 post-7 Gy γ-irradiation, compared to untreated controls.
Reduced the number of TUNEL-labeled apoptotic cells in the small intestine, testis, and spleen on Day 1 post-7 Gy γ-irradiation, compared to untreated controls.
Chemical Information
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CAS No. 74817-61-1
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Molecular Weight 548.58
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Formula C23H40N4O11
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SMILES
CC(N[C@@H](C=O)[C@H]([C@H](O)[C@H](O)CO)O[C@H](C)C(N[C@@H](C)C(N[C@H](CCC(N)=O)C(OCCCC)=O)=O)=O)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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Research Protocol for Infectious Diseases
Infectious-disease experiments test how pathogens interact with host barriers, innate immune receptors, inflammatory signaling, pathogen replication, and tissue injury; pattern-recognition receptors such as TLRs, RIG-I-like receptors, NOD-like receptors, and inflammasomes detect microbial molecules and activate NF-κB, interferon, and cytokine responses. The central hypothesis is that infection severity reflects the balance between pathogen burden and host response: protective inflammation restricts pathogen growth, whereas excessive or mislocalized inflammation contributes to tissue damage and disease phenotype. Unresolved questions include which host pathways are protective versus pathogenic, why some infection models fail to translate to human disease, and which combined readouts best predict clinically relevant infection outcomes.
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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
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Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
Purity & Documentation
References
[1]. Liu L, et al. NOD2 agonist murabutide alleviates radiation-induced injury through DNA damage response pathway mediated by ATR. Journal of cellular physiology. 2019 Nov;234(11):21294-21306. [Content Brief]
[2]. Truong MJ, et al. Differentially expressed genes in HIV-1-infected macrophages following treatment with the virus-suppressive immunomodulator murabutide. Virus research. 2004 Jan;99(1):25-33. [Content Brief]
[3]. Darcissac EC, et al. The synthetic immunomodulator murabutide controls human immunodeficiency virus type 1 replication at multiple levels in macrophages and dendritic cells. Journal of virology. 2000 Sep;74(17):7794-802. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Murabutide Related Classifications
HY-106055 Related Classifications
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