Promising Results from Hepatitis C Preclinical Studies
News Mar 07, 2012
BioCryst has successfully completed in vitro and in vivo studies in which BCX5191 exhibited potent and selective pan-genotypic antiviral activity against the hepatitis C polymerase enzyme. BCX5191 showed no inhibition of human RNA polymerase and no evidence of toxicity from standard in vitro screens.
Human liver cells rapidly and efficiently convert BCX5191 into its active triphosphate form. BCX5191 does not require prodrug technology to achieve bioavailability. BCX5191 inhibits the viral RNA polymerase enzyme across genotypes 1-4 at sub-micromolar concentrations (0.05-0.36 µM) and is active in replicon cell assays for genotypes 1a and 1b.
In preclinical models, BCX5191 demonstrates high oral bioavailability, and the drug is actively transported into the liver. Following a single oral dose in rats, liver BCX5191 triphosphate levels exceed the IC50 values for genotypes 1-4 through 24 hours. At Cmax, the drug triphosphate level is more than 100 times the IC50. This pharmacokinetic profile is expected to support once-daily dosing in clinical studies.
“BCX5191 has met stringent preclinical criteria to advance to IND-enabling studies. We expect this program to be ready to file for first-in-human studies during the fourth quarter of 2012,” said Dr. William P. Sheridan, Senior Vice President & Chief Medical Officer of BioCryst Pharmaceuticals. “Based on our internal comparative preclinical studies of BCX5191 with the most advanced nucleotide analog in clinical development, GS-7977, we believe BCX5191 has the potential to be the backbone of best-in-class oral treatment regimens for hepatitis C patients.”
Additional BCX5191 non-clinical experiments are ongoing or planned, including Good Laboratory Practices (GLP) non-clinical safety studies and in vitro evaluation of BCX5191 in combination with ribavirin.
Decoding the 3-D Structure of HuntingtinNews
Mutations on a single gene, the huntingtin gene, are the cause of Huntington's disease. They lead to an incorrect form of the correspondent protein. With the help of cryo-electron microscopy, researchers have now decoded the three-dimensional, molecular structure of the healthy human huntingtin protein.READ MORE
How Proteins Shape-Shift By the Hour is Central to Figuring Out How Circadian Clocks WorkNews
Scientists utilising X-ray crystallography and NMR spectroscopy have discovered that the way proteins move hour by hour is central to cyanobacteria's circadian clock function.READ MORE
Understanding the Process of Cell DivisionNews
Using multiple techniques such as structural modelling, X-ray scattering, X-ray crystallography and electron microscopy, scientists have found that the Spc110 protein provides a greater function in mitosis originally believed. This information could help understand the process in human cells and the abnormalities that occur in cancer.READ MORE
Comments | 0 ADD COMMENT
4th International Conference on Crystallography & Novel Materials
Nov 19 - Nov 20, 2018