Alisporivir

Alisporivir (Debio-025) is a cyclophilin inhibitor molecule with potent anti-hepatitis C virus ( HCV ) activity.

In Vitro

DEB025 binds to CypA, a peptidyl-prolyl cis-trans isomerase which is a crucial cofactor for HCV replication. Alisporivir (Debio-025) represents the prototype of a new class of non-immunosuppressive cyclophilin inhibitors. Alisporivir prevents HCV protein-mediated collapse of the respiration-driven mitochondrial membrane potential. Alisporivir prevents HCV protein-mediated mitochondrial dysfunction outside the context of apoptosis, calcium overload, production of ROS, dysfunction. In cell culture models, low-micromolar doses of alisporivir block SARS-CoV and MERS-CoV replication. Combination treatment with Alisporivir and ICN-1229 increases the anti-MERS-CoV activity in cell culture. Alisporivir pretreatment stimulates antigen presentation by hepatoma target cells, leading to enhancement of antigen-specific CD8+ T cell activation by 40%. Alisporivir induces an increase of MHC-I and beta-2 microglobulin on the surface of several cell lines . MCE has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Combination treatment with Alisporivir and ICN-1229 does not protect against SARS-CoV infection in a mouse model. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay

Alisporivir is prepared in DMSO at 4 mM and diluted in cell culture medium at the indicated concentrations (0.1, 0.2, 0.3, 0.4, 0.5 μM). UHCV-32 and UHCVcon-57.3 are U-2 OS human osteosar coma-derived cell lines inducibly expressing the entire open reading frame derived from the HCV H77 prototype and consensus clones, respectively. Cell viability is measured by trypan blue exclusion analysis. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Form:Solid