| CAS |
No.1092970-12-1 |
| 中文名称 |
莫非赛定 |
| 英文名称 |
Morphothiadin |
| 别名 |
GLS4 |
| 分子式 |
C21H22BrFN4O3S |
| 分子量 |
509.39 |
| 溶解性 |
Soluble in DMSO |
| 纯度 |
≥98% |
| 外观(性状) |
Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| SMILES |
CCOC(=O)C1=C(NC(=NC1C2=C(C=C(C=C2)F)Br)C3=NC=CS3)CN4CCOCC4 |
| InChIKey |
SQGRDKSRFFUBBU-UHFFFAOYSA-N |
| InChI |
InChI=1S/C21H22BrFN4O3S/c1-2-30-21(28)17-16(12-27-6-8-29-9-7-27)25-19(20-24-5-10-31-20)26-18(17)14-4-3-13(23)11-15(14)22/h3-5，10-11，18H，2，6-9，12H2，1H3，(H，25，26) |
| PubChem CID |
25144422 |
| 靶点 |
HBV |
| 通路 |
Anti-infection |
| 背景说明 |
Morphothiadin 是HBV 复制的有效抑制剂。 |
| 生物活性 |
Morphothiadin is a potent inhibitor on the replication of both wild-type and adefovir-resistant HBV with an IC50 of 12 nM.[1-2] |
| IC50 |
IC50: 12 nM (HBV)[1] |
| In Vitro |
Morphothiadin is a potent inhibitor on the replication of both wild-type and adefovir-resistant HBV with an IC50 of 12 nM. Morphothiadin (GLS4) shows no toxicity up to 25 μM. The cytotoxic dose whereby 50% of cells die (CC50) for primary hepatocytes is 115 μM for Morphothiadin (P90 is 190 μM for Morphothiadin (P[2]. |
| In Vivo |
The area under the concentration-time curve from 0 to 24 h (AUC0-24) of Morphothiadin (GLS4) is 556 h?ng/mL. After intravenous administration of 10 mg/kg Morphothiadin， the total plasma clearance and apparent volume distribution are 4.2 liters/h/kg and 7.38 liters/kg， respectively. The bioavailability of Morphothiadin is 25.5%. It is found that virus titers have increased 83.5-fold in mice treated with 3.75 mg/kg per day of Morphothiadin， 28.3-fold among mice treated with 7.5 mg/kg per day， but only 3- to 6-fold among mice treated with the higher doses of Morphothiadin. There is generally an inverse relationship between Morphothiadin dose and virus titer， with the greatest rebound seen in mice treated with 3.75 mg/kg per day of Morphothiadin (540-fold) and the smallest rebound in mice treated with 60 mg/kg per day (23-fold) (P7.5 mg/kg per day significantly suppresses the virus replication cycle throughout the treatment period， while Morphothiadin doses of >15 mg/kg per day suppresses virus for up to 2 weeks after the end of treatment[2]. |
| 细胞实验 |
HepAD38 cells are grown to about 80% confluence in 0.3 μg/mL of tetracycline (TET). After the removal of TET， the cells are treated with different doses of Morphothiadin (GLS4)， or no drug. Cell viability is monitored by 3-(4，5-dimethyl-2-thiazolyl)-2，5-diphenyl-2H-tetrazolium bromide (MTT) assay[2]. |
| 动物实验 |
ICR mice are used to evaluate the pharmacokinetic (PK) properties of Morphothiadin (GLS4). Following oral administration of 10 mg/kg (of body weight) of Morphothiadin to male mice， the concentration of Morphothiadin in plasma is determined using liquid chromatography-tandem mass spectrometry (LC/MS/MS). For toxicity studies， ICR mice are given Morphothiadin by gavage over a 4-week period and then kept off drug for another 2 weeks. Groups consisting of 20 male plus 20 female mice are administered a vehicle (1% methyl-2-hydroxyethyl cellulose)， 35.7， 118.9， or 356.6 mg/kg per day in a volume corresponding to 20 mL/kg. Ten mice per dose group are euthanized 2 weeks after the end of drug treatment. Body weight， food consumption， serum albumin levels， and adverse effects are determined[2]. |
| 数据来源文献 |
[1]. Zhou X， et al. Effects of ketoconazole and rifampicin on the pharmacokinetics of GLS4， a novel anti-hepatitis B virus compound， in dogs. Acta Pharmacol Sin. 2013 Nov;34(11):1420-6.
[2]. Wu G， et al. Preclinical characterization of GLS4， an inhibitor of hepatitis B virus core particle assembly. Antimicrob Agents Chemother. 2013 Nov;57(11):5344-54. |
| 规格 |
1mg 5mg 10mg |
| 单位 |
瓶 |
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