Carabrone

Carabrone is a sesquiterpene found in the fruits of Carpesium abrotanoides and acts as a STAT3 inhibitor (K_d = 25.23 nM) with antibacterial, antitumor, and orally active properties. Carabrone covalently binds to UBE2D3 via Cys85 (K_d = 3.85 μM) and inhibits IκBα phosphorylation and NF-κB signaling. Carabrone induces ROS accumulation, loss of mitochondrial membrane potential, DNA fragmentation, and metacaspase-1-mediated apoptosis in fungi. Carabrone ameliorates autoimmune encephalomyelitis and MASH in vivo, reduces pro-inflammatory cytokines without immunotoxicity. Carabrone is used in research related to autoimmune encephalomyelitis, steatohepatitis, and fungal infections^{[1][2][3][4][5]}. IC50 & Target:EC50: 7.10 μg/mL (Colletotrichum lagenarium)^[1] In Vitro:Carabrone (0.1 μM; 30 min-6 h) induces ROS production in Gaeumannomyces graminis (Ggt) hyphae^[1].
Carabrone (3.125-50 μg/mL) inhibits the activities of mitochondrial antioxidant enzymes GR, SOD, and CAT, while increasing the activity of GSH-PX and decreasing mitochondrial GSH content in Gaeumannomyces graminis (Ggt)^[1].
Carabrone (0.1 μM; 2-6 h) significantly reduces the mitochondrial membrane potential of Gaeumannomyces graminis (Get) mycelia^[1].
Carabrone (0.1 mM; ~6 h) undergoes a Michael addition reaction with L-cysteine (HY-Y0337) ^[1].
Carabrone (200 μM; 1 h) directly binds and stabilizes UBE2D3 in iBMDM whole-cell lysates^[2].
Carabrone (200 μM; 1 h) increases the thermal stability of endogenous UBE2D3 in iBMDMs and THP-1 cells^[2].
Carabrone (200 μM) protects endogenous UBE2D3 from proteolytic degradation in iBMDMs^[2].
Carabrone directly and potently binds to recombinant human UBE2D3 with a K_D of 3.85 μM^[2].
Carabrone is predicted to covalently bind to the Cys85 residue of UBE2D3 via a Michael addition reaction^[2].
Carabrone (50 µM; 4-6 h) directly binds to STAT3 in primary hepatocytes, as evidenced by decreased thermal stability^[3].
Carabrone (90 s) directly binds to STAT3 with a K_D value of 25.23 nM^[3].
Carabrone (4 h) specifically binds to STAT3, as confirmed by competitive pull-down experiments^[3].
Carabrone (0.1-1 µM) inhibits STAT3 activation in PO-stimulated hepatocytes^[3].
Carabrone (0.1-1 µM) inhibits STAT3 nuclear translocation in PO-stimulated primary hepatocytes^[3].
Carabrone inhibits STAT3 activation in PO-stimulated STAT3-knockdown L02 cells, and this inhibitory effect critically depends on Cys328^[3].
Carabrone inhibits the expression of MASH-related genes in PO-stimulated STAT3-knockdown L02 cells, and this inhibitory effect is critically dependent on Cys328^[3].
Carabrone (0.1 μM; 2-6 h) effectively induces apoptosis in Gaeumannomyces graminis (Ggt) and releases PS^[1].
Carabrone (0.1 μM; 0-48 h) induces DNA fragmentation in Gaeumannomyces graminis (Ggt)^[1].
Carabrone (0.1 μM; 0-48 h) upregulates the expression of metacaspase-1 genes Ggmet1 and Ggmet2 in Gaeumannomyces graminis (Get)^[1].
Carabrone (0-100 μM; 6 h) exhibits no cytotoxicity in iBMDMs and THP-1 cells at concentrations up to 20 μM, establishing a non-cytotoxic range for subsequent experiments^[2].
Carabrone (5-20 μM; 2 h) inhibits canonical NF-κB pathway activation in iBMDMs and THP-1 cells in a concentration-dependent manner^[2].
Carabrone (10-20 μM) inhibits LPS-induced nuclear translocation of NF-κB p65 in iBMDMs^[2].
Carabrone inhibits the NF-κB pathway in LPS (HY-D1056)-stimulated iBMDMs, and this inhibitory effect is abolished by pretreatment with β-mercaptoethanol (HY-Y0326), confirming the role of covalent cysteine binding^[2].
Carabrone (5-20 μM; 2 h) inhibits LPS-induced pro-inflammatory NF-κB target gene transcription in iBMDMs in a dose-dependent manner^[2].
Carabrone-mediated inhibition of the NF-κB signaling pathway in iBMDMs is specifically attenuated by Ube2d3 knockdown, indicating that its anti-inflammatory effect critically depends on the UBE2D3 protein^[2].
Carabrone (0.1-1 µM) alleviates lipid accumulation in PO-treated primary hepatocytes and L02 cells^[3].
Carabrone (0.1-1 µM) attenuates inflammation and fibrosis and modulates lipid metabolism gene expression in PO-treated primary hepatocytes and L02 cells^[3].
Carabrone (10 mg; 6-8 h) exhibits in vitro antifungal activity against Botrytis cinerea (IC₅₀ = 14.14 μg/mL) and Colletotrichum lagenarium (IC₅₀ = 8.29 μg/mL) in spore germination assays^[4].
Carabrone (5-100 μg/mL; 8 h) inhibits spore germination of Colletotrichum lagenarium with an EC₅₀ of 7.10 μg/mL^[5]. In Vivo:Carabrone (3-10 mg/kg/day; p.o.; daily; starting from day 3 post-immunization) significantly limits the development and severity of MOG_35-55 (HY-P1240)-induced EAE in mice, reduces clinical scores, CNS inflammatory infiltration, and demyelination, and modulates inflammatory signaling pathways in CD11b+ myeloid cells, particularly NF-κB^[2].
Carabrone (10 mg/kg; p.o.; daily; 21 days) does not cause significant immunotoxicity in C57BL/6 mice^[2].
Carabrone (1-10 mg/kg/day; p.o.; daily; 16 weeks) treatment alleviates HFHC diet-induced MASH by reducing lipid accumulation, inflammation, and fibrosis, and improving glucose metabolism^[3].
Carabrone (1-10 mg/kg/day; gavage; daily; 16 weeks) significantly ameliorates HFD-induced MASH by reducing lipid accumulation, liver injury, inflammation, and fibrosis, and improving glucose sensitivity^[3].
Carabrone (10 mg/kg/day; intragastric administration; daily; 8 weeks) alleviates MASH in MCD-fed mice in a STAT3-dependent manner, and its derivative CA-21 shows superior efficacy^[3].