First-in-human application of the novel hepatitis B and hepatitis D virus entry inhibitor myrcludex B

Blank, Antje; Markert, Christoph; Hohmann, Nicolas; Carls, Alexandra; Mikus, Gerd; Lehr, Thorsten; Alexandrov, Alexander I.; Haag, Mathias; Schwab, Matthias; Urban, Stephan; Haefeli, Walter E.

doi:10.1016/j.jhep.2016.04.013

Cited by 187 publications

(157 citation statements)

References 32 publications

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“…The success rate of these treatments is low. Several candidates are being evaluated in clinical trials mainly in combination with PegIFNa and/or NA including HBV/HDV entry inhibitors (Myrcludex-B), 244,245 drugs inhibiting the release of HBsAg (nucleic acid polymers), 246 and inhibitors of the prenylation of the large HDV antigen. 243,247 Whenever possible, enrollment in these new clinical trials should be considered, either as a rescue of PegIFNa failure or to improve treatment success rate in naïve patients.…”

Section: Future Treatment Options For Hdvmentioning

confidence: 99%

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

Lampertico¹,

Agarwal²,

Berg³

et al. 2017

Journal of Hepatology

4,184

3,081

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Section: Future Treatment Options For Hdvmentioning

confidence: 99%

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

Lampertico¹,

Agarwal²,

Berg³

et al. 2017

Journal of Hepatology

4,184

3,081

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“…1, the synthetic anti-lipopolysaccharide peptides (SALPs) inhibit HBV infection through binding to heparan sulfate moieties on the cell surface (Krepstakies et al, 2012). Myrcludex B is a HBV preS1-derived synthetic lipopoly-peptide that has been shown to specifically bind to NTCP and block de novo HBV infection and prevent intrahepatic viral spreading both in vitro and in vivo (Blank et al, 2016), and clinical trials to manage chronic HBV/HDV infection are well under way, and antiviral efficacy is being demonstrated (Bogomolov et al, 2016). Cyclosporin A (CsA) is an immunosuppressant that can directly bind to NTCP and interrupt the interaction between NTCP and the preS1 region (Watashi et al, 2014).…”

Section: Viral Binding and Entry Into Hepatocytesmentioning

confidence: 99%

Host functions used by hepatitis B virus to complete its life cycle: Implications for developing host-targeting agents to treat chronic hepatitis B

et al. 2018

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Similar to other mammalian viruses, the life cycle of hepatitis B virus (HBV) is heavily dependent upon and regulated by cellular (host) functions. These cellular functions can be generally placed in to two categories: (a) intrinsic host restriction factors and innate defenses, which must be evaded or repressed by the virus; and (b) gene products that provide functions necessary for the virus to complete its life cycle. Some of these functions may apply to all viruses, but some may be specific to HBV. In certain cases, the virus may depend upon the host function much more than does the host itself. Knowing which host functions regulate the different steps of a virus’ life cycle, can lead to new antiviral targets and help in developing novel treatment strategies, in addition to improving a fundamental understanding of viral pathogenesis. Therefore, in this review we will discuss known host factors which influence key steps of HBV life cycle, and further elucidate therapeutic interventions targeting host-HBV interactions.

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“…Beside the role of NTCP as major transporter for conjugated bile acids, NTCP was recently found to be the main receptor for HBV and HDV viral particles [31], and the specific NTCP inhibitor myrcludex B is currently being tested in phase II trials as an HBV/HDV entry inhibitor [32,33] (fig. 1).…”

Section: Ntcp As Receptor Of Hbv/hdvmentioning

confidence: 99%

Bile Acid Uptake Transporters as Targets for Therapy

Slijepćević¹,

Graaf²

2017

Dig Dis

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Background: Bile acids are potent signaling molecules that regulate glucose, lipid and energy homeostasis predominantly via the bile acid receptors farnesoid X receptor (FXR) and transmembrane G protein-coupled receptor 5 (TGR5). The sodium taurocholate cotransporting polypeptide (NTCP) and the apical sodium dependent bile acid transporter (ASBT) ensure an effective circulation of (conjugated) bile acids. The modulation of these transport proteins affects bile acid localization, dynamics and signaling. The NTCP-specific pharmacological inhibitor myrcludex B inhibits hepatic uptake of conjugated bile acids. Multiple ASBT-inhibitors are already in clinical trials to inhibit intestinal bile acid uptake. Here, we discuss current insights into the consequences of targeting bile acid uptake transporters on systemic and intestinal bile acid dynamics and discuss the possible therapeutic applications that evolve as a result.

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First-in-human application of the novel hepatitis B and hepatitis D virus entry inhibitor myrcludex B

Cited by 187 publications

References 32 publications

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

Host functions used by hepatitis B virus to complete its life cycle: Implications for developing host-targeting agents to treat chronic hepatitis B

Bile Acid Uptake Transporters as Targets for Therapy

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