Tilorone dihydrochloride
(Synonyms: 盐酸替洛隆；梯洛龙二盐酸盐；替洛隆二盐酸盐；盐酸梯洛龙) 目录号 : GC32228
An interferon-inducing antiviral agent
Cas No.:27591-69-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Tilorone is an orally active, antiviral compound that induces interferon production and is reported to have antitumor, anti-inflammatory, and neuroprotective actions.1,2,3 With chronic administration, tilorone induces lysosomal glycosaminoglycan storage, rendering glycosaminoglycans resistant to enzymatic degradation.4
1.Stringfellow, D.A., and Glasgow, L.A.Tilorone hydrochloride: An oral interferon-inducing agentAntimicrob. Agents Chemother.2(2)73-78(1972) 2.Wissing, M.D., Dadon, T., Kim, E., et al.Small-molecule screening of PC3 prostate cancer cells identifies tilorone dihydrochloride to selectively inhibit cell growth based on cyclin-dependent kinase 5 expressionOncol. Rep.32419-424(2014) 3.Ratan, R.R., Siddiq, A., Aminova, L., et al.Small molecule activation of adaptive gene expression: Tilorone or its analogs are novel potent activators of hypoxia inducible factor-1 that provide prophylaxis against stroke and spinal cord injuryAnn. N. Y. Acad. Sci.1147383-394(2011) 4.Fischer, J.Tilorone-induced lysosomal storage of glycosaminoglycans in cultured corneal fibroblasts: Biochemical and physicochemical investigationsBiochem. J.312215-222(1995)
| Cas No. | 27591-69-1 | SDF | |
| 别名 | 盐酸替洛隆；梯洛龙二盐酸盐；替洛隆二盐酸盐；盐酸梯洛龙 | ||
| Canonical SMILES | O=C1C2=C(C3=C1C=C(OCCN(CC)CC)C=C3)C=CC(OCCN(CC)CC)=C2.[H]Cl.[H]Cl | ||
| 分子式 | C25H36Cl2N2O3 | 分子量 | 483.47 |
| 溶解度 | Water : ≥ 28 mg/mL (57.91 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0684 mL | 10.3419 mL | 20.6838 mL |
| 5 mM | 0.4137 mL | 2.0684 mL | 4.1368 mL |
| 10 mM | 0.2068 mL | 1.0342 mL | 2.0684 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Efficacy of Tilorone dihydrochloride against Ebola Virus Infection
Antimicrob Agents Chemother 2018 Jan 25;62(2):e01711-17.PMID:29133569DOI:10.1128/AAC.01711-17.
Tilorone dihydrochloride (tilorone) is a small-molecule, orally bioavailable drug that is used clinically as an antiviral outside the United States. A machine-learning model trained on anti-Ebola virus (EBOV) screening data previously identified tilorone as a potent in vitro EBOV inhibitor, making it a candidate for the treatment of Ebola virus disease (EVD). In the present study, a series of in vitro ADMET (absorption, distribution, metabolism, excretion, toxicity) assays demonstrated the drug has excellent solubility, high Caco-2 permeability, was not a P-glycoprotein substrate, and had no inhibitory activity against five human CYP450 enzymes (3A4, 2D6, 2C19, 2C9, and 1A2). 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. A pharmacokinetics study in mice at 2- and 10-mg/kg dose levels showed that the drug is rapidly absorbed, has dose-dependent increases in maximum concentration of unbound drug in plasma and areas under the concentration-time curve, and has a half-life of approximately 18 h in both males and females, although the exposure was 鈭?.5-fold higher in male mice. 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. A subsequent study showed that 30 mg/kg/day of tilorone given i.p. starting 2 or 24 h postchallenge and continuing through day 7 postinfection was fully protective, indicating promising activity for the treatment of EVD.
An Effective Synthesis Method for Tilorone dihydrochloride with Obvious IFN-伪 Inducing Activity
Molecules 2015 Dec 2;20(12):21458-63.PMID:26633340DOI:10.3390/molecules201219781.
Tilorone dihydrochloride (1) has great potential for inducing interferon against pathogenic infection. In this paper, we describe a convenient preparation method for 2,7-dihydroxyfluoren-9-one (2), which is a usual pharmaceutical intermediate for preparing Tilorone dihydrochloride (1). In the novel method, methyl esterification of 4,4'-dihydroxy-[1,1'-biphenyl]-2-carboxylic acid (4) was carried out under milder conditions with higher yield and played an important role in the preparation of compound 2. The structures of the relative intermediates and target compound were characterized by melting point, IR, MS, and 鹿H-NMR. Furthermore, the synthesized Tilorone dihydrochloride exhibited an obvious effect on induction of interferon-伪 (IFN-伪) in mice within 12 h, and the peak level was observed until 24 h. This fruitful work has resulted in Tilorone dihydrochloride becoming available in large-scale and wide application in clinics, which has a good pharmaceutical development prospects.
The effects of coadministration of Tilorone dihydrochloride and culture supernatants from Lactobacillus reuteri on the mouse hepatoma cell line
J Cancer Res Ther 2019 Jan-Mar;15(1):176-184.PMID:30880776DOI:10.4103/jcrt.JCRT_41_17.
Context: Tilorone dihydrochloride is a therapeutic agent with a different mechanism in cancer. The species of Lactobacillus have an important role in cytotoxic effect. Aims: Because of unknown effects of tilorone and culture supernatants from Lactobacillus reuteri on hepatoma, the aim of this study is to evaluate apoptotic, cytotoxic, and therapeutic effects of tilorone on mouse hepatoma cell line with and without culture supernatants from L. reuteri. Materials and methods: To do so, after cell line culture, cells were divided into different groups such as negative control, treatment with four doses of tilorone, positive control of supernatant (single dose), and combination therapy groups of different doses of tilorone with supernatant (constant doses), for 48 h. All groups were studied with pathologic tests, biochemical study, tetrazolium dye (3-(4, 5- dimethylthiazol -2-yl)-2, 5-diphenyltetrazolium bromide [MTT]) assay, and absolute real-time-polymerase chain reaction (RT-PCR) were done to assess Bax and Bcl-2 genes expression, as molecular studies. Results: MTT assay results revealed that the tilorone tissue culture IC50 (TCIC50) on the Hepa1-6 cell line was 50 渭g/ml. RT-PCR analysis showed that Tilorone dihydrochloride induced upregulation and downregulation in expression of Bax and Bcl-2, respectively. Simultaneous, antioxidant effect has also seen in a way that prevented necrosis, in biochemical analysis. These results were dose dependent and statistically significant compared to the control group. Conclusions: Based on these results, it appeared that this agent could be a good candidate for further evaluation as effective chemotherapy acting through the induction of apoptosis in hepatoma. The cell death caused through bacterial supernatant was rather necrosis than apoptosis.
Tilorone confers robust in vitro and in vivo antiviral effects against severe fever with thrombocytopenia syndrome virus
Virol Sin 2022 Feb;37(1):145-148.PMID:35234618DOI:10.1016/j.virs.2022.01.014.
鈥? Tilorone dihydrochloride possesses robust anti-SFTSV activity in vitro and in vivo. 鈥? Intraperitoneal administration of tilorone leads to protection against intracranial lethal challenge of SFTSV. 鈥? The anti-SFTSV mechanism of tilorone is through stimulation of host innate immunity. 鈥? Pre-treatment with tilorone can prevent mice from lethal SFTSV challenge.
New synthetic routes to Tilorone dihydrochloride and some of its analogues
J Med Chem 1978 Oct;21(10):1084-6.PMID:722716DOI:10.1021/jm00208a016.
New synthetic routes to the orally active, interferon-inducing antiviral agent Tilorone dihydrochloride, 2,7-bis-[(diethylamino)ethoxy]fluoren-9-one dihydrochloride (1a), were developed. The routes involved the preparation and solvolysis of tetrazonium fluoroborate salts of 2,7-diaminofluoren-9-one. Nonplanar (1b), 9-sulfone (1c), and fluorene (1d) analogues of Tilorone dihydrochloride were also prepared. Compounds 1b and 1c were evaluated for interferon induction.