Tilorone (dihydrochloride)

Tilorone dihydrochloride is an orally active interferon (IFN) inducer with broad-spectrum antiviral activities. Tilorone dihydrochloride possesses robust anti-Severe fever with thrombocytopenia syndrome virus (SFTSV) activity in vitro and in vivo through stimulation of host innate immunity. Tilorone dihydrochloride can penetrate the blood-brain barrier to activate HIF in the CNS^[1][2][3].Tilorone dihydrochloride exhibits an inhibitory activity with EC₅₀ of 230 nM against Ebola virus (EBOV)^[4]. In Vitro:Tilorone (0.1, 0.3, 1 μM) dihydrochloride inhibits SFTSV-induced cytopathological effect (CPE) in a dose-dependent manner with no cell toxicity in Huh7 cells^[1].
Tilorone dihydrochloride reveals drug-like properties, with solubility of 465 μM at pH 7.4, stable mouse microsomal metabolity (half-time: 47.8 min; CL: 14.5 μL/min/mg) and Caco-2 permeability (10 μM) of 20.4×10^-6 cm/s and 8.87×10^-6 cm/s^[4].
In Vivo:Tilorone (5-20 mg/kg; intraperitoneally; once daily at 1-7 days) dihydrochloride with 20 mg/kg protects 78.94% of the mice from lethal challenge with virus intracranially^[1].
Tilorone (5, 10 mg/kg; intraperitoneally; 12 h prior to challenge, at the time point of challenge, and 12 h after challenge) dihydrochloride with 10 mg/kg dose-dependently inhibits viremia, causes a general increase in IFN-α and IFN-β, reduces the TNF-α and IL-10 in a viremia model based on wild-type 6-week-old female BALB/c mice with SFTSV^[1].
Tilorone dihydrochloride (10-50 mg/kg, i.p., once daily for 8 days) exhibits a dose-efficient range against EBOV of 25-50 mg/kg, with full clearance of virus in mice^[4].
Tilorone dihydrochloride (30-60 mg/kg, i.p., once, 2 h , 24 h and 48 h postinfection) reveals 100% survival rate at dosage of 30 mg/kg in BALB/c mice, when dosed at 2 h and 24 h postinfection^[4]. Tilorone dihydrochloride (2-10 mg/kg, once, i.p.) reveals a pharmacokinetic parameter in BLAB/c mice ^[4]:

Pharmacokinetic Analysis of Tilorone in BALB/c mice^[1]

Dose (mg/kg)	Sex	T1/2 (h)	Tmax (h)	Cmax (ng/ml)	AUClast (ng·h/ml)	AUCinf (ng·h/ml)	CLblood (ml/h/kg)	V (ml/kg)
2	M	15.7	0.083	50.5	356	516	87900	3870
2	F	18.7	0.083	17.5	133	210	257000	9510
10	M	20.8	0.25	135	1099	1940	155000	5160
10	F	18.9	0.25	92.3	513	793	343000	12600