Tilorone dihydrochloride (tilorone) is a small-molecule, orally bioavailable drug. Tilorone was shown to have 52% human plasma protein binding with excellent plasma stability and a mouse liver microsome half-life of 48 min. Dose range-finding studies in mice demonstrated a maximum tolerated single dose of 100 mg/kg of body weight. Tilorone doses of 25 and 50 mg/kg proved efficacious in protecting 90% of mice from a lethal challenge with mouse-adapted with once-daily intraperitoneal (i.p.) dosing for 8 days[3]. RT-PCR analysis showed that tilorone dihydrochloride induced upregulation and downregulation in expression of Bax and Bcl-2, respectively[4]. Furthermore, the synthesized tilorone dihydrochloride exhibited an obvious effect on induction of interferon-α (IFN-α) in mice within 12 h, and the peak level was observed until 24 h[5]. Moreover, tilorone treatment resulted in decreased PC3 cell growth and invasion; PC3 cells with inactive CDK5 (Cyclin-dependent kinase 5) were inhibited more effectively[6].
Tilorone 2HCl/替洛隆 二盐酸盐 细胞实验
Cell Line
Concentration
Treated Time
Description
References
A549 cells
6.31 µM
24 hours
Evaluate the inhibitory effect of Tilorone on RVFV ZH501, showing an EC50 of 6.31 μM
Microorganisms. 2021 Dec 31;10(1):92
Vero CCL81 cells
6.45 µM
24 hours
Evaluate the inhibitory effect of Tilorone on RVFV ZH501, showing an EC50 of 6.45 μM
Microorganisms. 2021 Dec 31;10(1):92
A549 cells
1.41 µM
24 hours
Evaluate the inhibitory effect of Tilorone on RVFV MP-12, showing an EC50 of 1.41 μM
Microorganisms. 2021 Dec 31;10(1):92
Vero CCL81 cells
0.67 µM
24 hours
Evaluate the inhibitory effect of Tilorone on RVFV MP-12, showing an EC50 of 0.67 μM
Microorganisms. 2021 Dec 31;10(1):92
Human midbrain-like organoids
0.5 µM to 4 µM
48 hours
Assess the effect of Tilorone on the uptake of α-syn fibrils and apoptosis. Results showed that Tilorone reduced the uptake of α-syn fibrils and mitigated α-syn fibril-induced apoptosis. Furthermore, Tilorone reduced sPFF-induced endogenous α-syn phosphorylation.
J Transl Med. 2024 Sep 2;22(1):816
Bovine corneal fibroblasts
5 µM
96 hours
Investigation of tilorone-induced lysosomal storage of glycosaminoglycans (GAGs), showing predominant accumulation of dermatan sulfate (DS), accounting for over 90% of intracellular GAG storage.
Biochem J. 1995 Nov 15;312 ( Pt 1)(Pt 1):215-22
Mouse primary hippocampal neurons
0.5 µM to 2 µM
two weeks
Evaluate the effect of Tilorone on the uptake of α-syn fibrils and endogenous α-syn phosphorylation. Results showed that Tilorone reduced the uptake of α-syn fibrils in a dose-dependent manner, with maximal inhibition observed at 2 µM. Additionally, Tilorone reduced sPFF-induced endogenous α-syn phosphorylation.
J Transl Med. 2024 Sep 2;22(1):816
Tilorone 2HCl/替洛隆 二盐酸盐 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
ICR mice
Lethal virus challenge model
Intraperitoneal injection
20 mg/kg
Once daily for 7 days
To evaluate the in vivo antiviral efficacy of tilorone against SFTSV, results showed that 20 mg/kg tilorone protected 78.94% of mice from lethal challenge
Virol Sin. 2022 Feb;37(1):145-148
CD-1 mice
VEEV infection model
Intragastric
25.6 mg/kg
Once daily for 10 days
Tilorone significantly reduced viremia in mice and protected them from death
Pharmaceuticals (Basel). 2022 May 17;15(5):617
Mice
SPF mice
Oral
250 mg/kg
Single dose, observed for 24 hours
To evaluate the IFN-α inducing activity of tilorone dihydrochloride, showing peak levels (approximately 2000 pg/mL) at 12 to 24 hours post-administration.
Molecules. 2015 Dec 2;20(12):21458-63
BALB/c mice
RVFV ZH501 infection model
Intraperitoneal injection
30 mg/kg/day or 60 mg/kg/day
Once daily for 9 days
Evaluate the in vivo protective effect of Tilorone against RVFV ZH501 infection, showing 80% survival at 30 mg/kg/day
Microorganisms. 2021 Dec 31;10(1):92
Mice
CD-1 mice
Oral
75 mg/kg
Single dose
To study the effect of Tilorone on the expression of xanthine dehydrogenase (XD) mRNA in mouse liver. Results showed that Tilorone increased the expression of XD mRNA.
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