Structure of Fraxinellone
CAS No.: 28808-62-0
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Fraxinellone, a natural product isolated and purified from the root barks of Dictamnus dasycarpus Turcz. with neuroprotective, vasorelaxing, insecticidal, and antimicrobial activities, is a selective blocker of voltage-dependent Ca2+ channel, while dictamine relaxed the rat aorta by suppressing the Ca2+ influx through both voltage-dependent and receptor-operated Ca2+ channels, and can dramatically induce apoptosis of activated peripheral CD4(+) T cells in vivo, consequently resulting in less CD4(+) T-cell activation and infiltration to the liver.
Synonyms: Fraxinellone
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CAS No. : | 28808-62-0 |
Formula : | C14H16O3 |
M.W : | 232.28 |
SMILES Code : | CC(CCC[C@]1([C@](O2)([H])C3=COC=C3)C)=C1C2=O |
Synonyms : |
Fraxinellone
|
MDL No. : | MFCD11101451 |
InChI Key : | XYYAFLHHHZVPRN-GXTWGEPZSA-N |
Pubchem ID : | 124039 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
In Vitro:
Cell Line
|
Concentration | Treated Time | Description | References |
HT-29 cells | 3, 10, 30 μM | 24 hours | Inhibited TGF-β-induced fibrosis responses by inhibiting the TGF-β/Smad2/3 signaling pathway. | Acta Pharmacol Sin. 2023 Dec;44(12):2469-2478 |
SW480 cells | 3, 10, 30 μM | 24 hours | Inhibited TGF-β-induced fibrosis responses by inhibiting the TGF-β/Smad2/3 signaling pathway. | Acta Pharmacol Sin. 2023 Dec;44(12):2469-2478 |
Human peripheral blood mononuclear cells | 40 μM | 4 days | To evaluate the effect of fraxinellone on human osteoclast differentiation. Results showed that fraxinellone significantly reduced the number of TRAP-positive multinucleated cells and decreased the expression of MMP9, RANK, cathepsin K, integrin β3, and NFATc1. | Int J Mol Sci. 2018 Mar 13;19(3):829 |
Murine bone marrow-derived monocytes | 10-40 μM | 4 days | To evaluate the effect of fraxinellone on osteoclast formation. Results showed that fraxinellone inhibited the formation of TRAP-positive multinucleated cells in a dose-dependent manner and significantly reduced the expression of TRAP, cathepsin K, and MMP9. | Int J Mol Sci. 2018 Mar 13;19(3):829 |
CD19+ B cells | 40 μM | 4 days | To evaluate the effect of fraxinellone on B cell function. Results showed that fraxinellone significantly reduced the expression of AID and Blimp-1 and decreased the production of immunoglobulin G. | Int J Mol Sci. 2018 Mar 13;19(3):829 |
CD4+ T cells | 30-50 μM | 3 days | To evaluate the effect of fraxinellone on Th17 differentiation. Results showed that fraxinellone reduced the proportion of CD4+IL-17+ cells in a dose-dependent manner and significantly decreased the expression of IL-17 and RORγt. | Int J Mol Sci. 2018 Mar 13;19(3):829 |
SCC2095 cells | 28.6 μg/ml (IC50) | 48 hours | Evaluate the anti-proliferation activity of Fraxinellone against oral squamous cell carcinoma cells, showing an IC50 of 28.6 μg/ml, significantly lower than that of ZSP (>500 μg/ml) | J Ethnopharmacol. 2015 Aug 22;172:195-201 |
SH-SY5Y cells | ≤1 μM | 30 minutes | Evaluate the protective effect of Fraxinellone against glutamate toxicity, results showed no significant protection at ≤1 μM | ACS Chem Neurosci. 2024 Jul 17;15(14):2612-2622 |
PC12 cells | ≤1 μM | 30 minutes | Evaluate the protective effect of Fraxinellone against glutamate toxicity, results showed no significant protection at ≤1 μM | ACS Chem Neurosci. 2024 Jul 17;15(14):2612-2622 |
human hypertrophic scar-derived fibroblasts (HSFs) | 100 µM, 200 µM, 300 µM | 48 hours | To evaluate the effect of FRA on the proliferation and migration capacity of HSFs. Results showed that FRA significantly suppressed the proliferation and migration of HSFs. | Biol Direct. 2025 Feb 4;20(1):17 |
human osteosarcoma cell line MG63 | 0-320μM | 0-48 hours | FRA inhibited the proliferation and migration of MG63 cells in a dose-dependent manner | Front Pharmacol. 2021 Apr 19;12:653212 |
human osteosarcoma cell line HOS | 0-320μM | 0-48 hours | FRA inhibited the proliferation and migration of HOS cells in a dose-dependent manner | Front Pharmacol. 2021 Apr 19;12:653212 |
In Vivo:
Species
|
Animal Model
|
Administration | Dosage | Frequency | Description | References |
C57BL/6 mice | Bile duct ligation (BDL)-induced liver fibrosis | Gavage | 10, 20, 40 mg/kg | Once daily for 4 weeks | Fraxinellone significantly ameliorated BDL-induced liver fibrosis, including reduced collagen deposition, serum hyaluronic acid, laminin, and type III procollagen levels, as well as liver hydroxyproline content. | Nat Commun. 2016 Nov 17;7:13498 |
C57BL/6 mice | DSS-induced intestinal fibrosis model | Intragastric administration | 7.5, 15, 30 mg/kg/d | Once daily for 45 days | Dose-dependently alleviated DSS-induced intestinal impairments and reduced the production of intestinal fibrosis biomarkers. | Acta Pharmacol Sin. 2023 Dec;44(12):2469-2478 |
DBA/1J mice | Collagen-induced arthritis (CIA) model | Intraperitoneal injection | 7.5 mg/kg | Three times per week for eight weeks | To evaluate the therapeutic effect of fraxinellone on inflammatory arthritis. Results showed that fraxinellone significantly attenuated the clinical and histologic features of arthritis, reduced serum IgG levels, and inhibited the production of TNF-α and IFN-γ. | Int J Mol Sci. 2018 Mar 13;19(3):829 |
New Zealand white rabbits | Rabbit ear scar model | Subcutaneous injection | 100 µM, 300 µM | Every other day for 14 days | To validate the therapeutic efficacy of FRA on scar formation in vivo. Results showed that FRA significantly attenuated scar formation and improved collagen fiber arrangement. | Biol Direct. 2025 Feb 4;20(1):17 |
Nude mice | Osteosarcoma xenograft model | Gavage | 50 mg/kg and 100 mg/kg | Once daily for 21 days | FRA treatment inhibited the growth of osteosarcoma, and the pro-apoptotic and autophagy effects of FRA were also proved in vivo | Front Pharmacol. 2021 Apr 19;12:653212 |
Zebrafish | Zebrafish larvae | Culture medium exposure | 10–30 μM | 48 hours | To evaluate the hepatotoxicity of FRA and its mechanism, the results showed that FRA induces apoptosis by increasing the level of ROS and activating the JNK/P53 pathway, and induces cholestasis by down-regulating bile acid transporters P-gp, Bsep, and Ntcp. | Molecules. 2022 Apr 20;27(9):2647 |
Tags: Fraxinellone | PD-1/PD-L1 | HIF/HIF Prolyl-Hydroxylase | STAT | PD-1/Programmed death-ligand 1 | Hypoxia-inducible factors | HIFs | HIF-PH | inhibitor | 28808-62-0 |
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