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This article is part of the supplement: 2006 International Meeting of The Institute of Human Virology

Open Access Oral presentation

The chemistry and biology of KP-1461, a selective nucleoside mutagen for HIV therapy

Kevin Harris, Dmitri Sergueev and John Reno*

Author Affiliations

Koronis Pharmaceuticals, Inc., Redmond, Washington, 98052, USA

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Retrovirology 2006, 3(Suppl 1):S13  doi:10.1186/1742-4690-3-S1-S13

The electronic version of this article is the complete one and can be found online at:


Published:21 December 2006

© 2006 Harris et al; licensee BioMed Central Ltd.

Oral presentation

KP-1461 is a deoxycytidine analogue that is randomly inserted into HIV DNA by reverse transcriptase where it can cause base mispairing and introduce mutations that decrease viral fitness. The nucleoside consists of a natural deoxyribose for efficient use by the viral polymerase and a modified base that undergoes tautomerization between a cytosine form and a thymine form that exclusively causes transitional mutations. In vitro testing showed ablation of HIV when used in a serial passage format [1]. Host cell nuclear polymerases alpha and beta have a high Km for KP-1461 triphosphate that could preclude incorporation into nuclear DNA. KP-1461 has successfully completed preclinical testing including animal toxicology studies, a complete panel of genotoxicity assessments, and acute cardio, pulmonary and neurotoxicity tests. A single dose Phase 1a clinical trial in healthy volunteers showed safety and PK to continue clinical development. A Phase 1b study is currently underway in ARV-experienced HIV+ patients.

References

  1. Harris KS, Brabant W, Styrchak S, Gall A: Daifuku R KP-1212/1461, a nucleoside designed for the treatment of HIV by viral mutagenesis.

    Antiviral Res 2005, 67:1-9. PubMed Abstract | Publisher Full Text OpenURL