- |||||||||| lamivudine HBV / Generic mfg.
Journal: Discovery of carboxyl-containing heteroaryldihydropyrimidine derivatives as novel HBV capsid assembly modulators with significantly improved metabolic stability. (Pubmed Central) - Nov 17, 2023 The results from biological evaluation demonstrated that compound 6a-25 (EC = 0.020 ?M) exhibited greater potency than the positive drug lamivudine (EC = 0.09 ?M), and was comparable to the lead compound GLS4 (EC = 0.007 ?M)...Preliminary assessment of drug-likeness revealed that 6a-25 exhibited superior water solubility (pH 2.0: 374.81 ?g mL; pH 7.0: 6.85 ?g mL; pH 7.4: 25.48 ?g mL), liver microsomal metabolic stability (t = 108.2 min), and lower hERG toxicity (10 ?M inhibition rate was 72.66%) compared to the lead compound GLS4. Overall, compound 6a-25 holds promise for further investigation.
- |||||||||| morphothiadine mesilate (GLS4) / HEC Pharm
Journal: Design, Synthesis, and Biological Evaluation of Novel Thioureidobenzamide (TBA) Derivatives as HBV Capsid Assembly Modulators. (Pubmed Central) - Oct 15, 2023 Moreover, 17i displayed a better inhibitory effect on the assembly of HBV capsid protein compared with NVR 3-778 and a inhibitory effect similar to the clinical drug GLS4. In addition, 17i showed moderate metabolic stability in human microsomes, had excellent oral bioavailability in Sprague-Dawley (SD) rats, and inhibited HBV replication in the HBV carrier mice model, which could be considered as a promising candidate drug for further development.
- |||||||||| morphothiadine mesilate (GLS4) / HEC Pharm
Trial completion date, Trial primary completion date, Combination therapy: Evaluate the Safety, Tolerability, and Antiviral Activity of GLS4 With Ritonavir in Patients With Chronic HBV Infection (clinicaltrials.gov) - Apr 12, 2023 P2, N=250, Recruiting, In addition, 17i showed moderate metabolic stability in human microsomes, had excellent oral bioavailability in Sprague-Dawley (SD) rats, and inhibited HBV replication in the HBV carrier mice model, which could be considered as a promising candidate drug for further development. Trial completion date: Oct 2022 --> May 2023 | Trial primary completion date: Feb 2022 --> May 2023
- |||||||||| morphothiadine mesilate (GLS4) / HEC Pharm
Computational prediction of susceptibility and resistance for HBV capsid assembly effectors (Hall F2 (McCormick Place Convention Center)) - Aug 9, 2022 - Abstract #ACSFall2022ACS_Fall_9079; The results also suggest that GLP-26 will possess broad anti-HBV activity, more so than GLS4. This study demonstrates the utility of computational resistance prediction in the context of drug discovery, which can be applied to many viral protiens.
- |||||||||| HEC121120 / HEC Pharm
HEC121120, a novel allosteric modulator of HBV core protein demonstrates potent antiviral activities in vitro and in vivo (Poster Area) - Mar 16, 2022 - Abstract #EASLILC2022EASL_ILC_1763; In PHH isolated from chronically infected humanized liver mouse, 14 days of GLS4 (5 μM) and HEC121120 (2 μM) treatment resulted in suppression of HBV DNA, HBsAg and HBeAg while entecavir (ETV) had no effect on either viral antigen. HEC121120 is a novel class I CAM, which demonstrated improved antiviral properties both in vitro and in vivo, further clinical study will be conducted to evaluate the antiviral potency in CHB patients.
- |||||||||| lamivudine HBV / Generic mfg.
Journal: Design, synthesis and evaluation of heteroaryldihydropyrimidine analogues bearing spiro ring as hepatitis B virus capsid protein inhibitors. (Pubmed Central) - Jan 14, 2022 Potent in vitroanti-HBV activity and low cytotoxicity were observed for compound 4r (EC = 0.20 ± 0.00 μM, CC > 87.03 μM), which was more potent than the positive control lamivudine (EC = 0.37 ± 0.04 μM, CC > 100.00 μM) in this assay and was about a quarter as effective as GLS4 (EC = 0.045 ± 0.01 μM, CC > 99.20 μM)...In terms of the physicochemical properties, 4r was predicted to be consistent with the rule-of-five, which means 4r may have favourable absorption and permeation. Finally, ADMET and PK characteristics of 4r and GLS4 were predicted to be comparable in most aspects, implying that the two compounds may have similar profiles in vivo.
- |||||||||| morphothiadine mesilate (GLS4) / HEC Pharm
Trial completion: GLS4/RTV and TAF Drug-drug Interaction (clinicaltrials.gov) - May 9, 2021 P1, N=28, Completed, The preliminary structure-activity relationships (SARs) of the new compounds were summarized, which may help in discovering more potent anti-HBV agents via rational drug design. Not yet recruiting --> Completed
- |||||||||| morphothiadine mesilate (GLS4) / HEC Pharm
Trial completion: The Safety, Antiviral Activity, and Pharmacokinetics of Morphothiadine Mesilate Capsules (clinicaltrials.gov) - Jul 23, 2020 P2, N=20, Completed, Interim results showed that the antiviral efficacy of combination therapy of GLS4/RTV with ETV is remarkably superior to ETV monotherapy, further studies are ongoing to evaluate the safety and efficacy of the combination therapy. Recruiting --> Completed
- |||||||||| lamivudine / Generic mfg., ATI-2173 / Antios Therap
[VIRTUAL] ATI-2173, a novel phosphoramidate nucleoside prodrug for HBV cure regimens (Poster Area) - May 30, 2020 - Abstract #EASLILCI2020EASL-ILC-I-1825; ATI-2173 is a potent liver-targeted molecule that delivers the 5’-monophosphate of clevudine, enhancing the anti-HBV activity while significantly reducing systemic exposure to clevudine in the rat and monkey. ATI-2173 combined with TDF, ETV or other direct acting antivirals, could become an integral part of combination HBV cure regimens.
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