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^[1][2][3]. 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]. In Vivo:Murabutide (300 μg/mouse; i.p.; single dose; 2 hours before irradiation) pretreatment improves survival (20% survival at 8.5 Gy, 50% survival at 7 Gy over 30 days) and alleviates radiation-induced tissue damage and apoptosis in male C57BL/6 mice^[1].