GLS4

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

GLS4 (Morpothiadin) 是 HBV 衣壳组装的有效抑制剂，抑制 HBV 复制 (EC50=62.24 nM) 并降低 HepG.2.2.15 细胞中的 HBV-DNA 水平 (IC50=14 nM)。

GLS4 (Morphothiadin) is a potent inhibitor of HBV capsid assembly, inhibits HBV replication (EC50=62.24 nM) and reduces HBV-DNA levels in HepG.2.2.15 cells (IC50=14 nM), shows efficacy against ADV-resistant HBV mutations; strongly inhibits core gene expression (at 100 to 200 nM), suppresses virus accumulation in the supernantant of HepAD38 cells; inhibits HBV replicative forms in the live, shows strong and sustained suppression of virus DNA in treated mice.HBV Infection Phase 3 Clinical.

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 (P<0.001). The CC90 is 190 μM for Morphothiadin (P<0.01) in HepAD38 cells. Morphothiadin strongly inhibits virus accumulation in the supernatant of HepAD38 cells at 25 nM to 100 nM (P<0.02). Results show a concentration-dependent decrease of core protein in cells treated with Morphothiadin.

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) (P<0.001). The Morphothiadin doses of >7.5 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.

GLS 4 | Morphothiadin

Microbiology/Virology

HBV

HBV

Infection

HBV Infection

1092970-12-1

509.394

C21H22BrFN4O3S

>98% (HPLC)

DMSO : 100 mg/mL 196.31 mM; H2O : < 0.1 mg/mL

CCOC(=O)C1=C(NC(=NC1C2=C(C=C(C=C2)F)Br)C3=NC=CS3)CN4CCOCC4

ethyl 4-(2-bromo-4-fluorophenyl)-6-(morpholinomethyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate

(-20℃)

With Ice Pack

≥ 2 years