Abstract
Introduction: Boceprevir was the first direct acting agent developed for the treatment of hepatitis C virus infection. Boceprevir functions by targeting NS3 protease, a viral enzyme essential for replication. This peptidomimetic molecule was optimized from a peptide lead to provide a potent, selective and orally bioavailable drug that can be combined with ribavirin and peg interferon to achieve sustained viral response (undetectable HCV RNA levels for 24 weeks after completion of therapy) in patients infected with Genotype 1 of the virus. Areas covered: This article provides a review of the pre-clinical and clinical discovery of boceprevir. This review includes the role and function of its molecular target, NS3 protease, as well as the assays used to measure in vitro efficacy, compound optimization and clinical studies to demonstrate safety and efficacy. Expert opinion: As the first direct acting anti-HCV agent, boceprevir represents an important advance in therapy of this widespread chronic disease. Yet, while this therapy is a valuable approach, it does have limitations. Studies have suggested that 30% of patients do not achieve sustained viral response and 11% of patients have developed anemia and/or neutropenia. Current drug discovery and development efforts are underway to develop novel therapeutic options that address these issues.
| Original language | English |
|---|---|
| Pages (from-to) | 1439-1447 |
| Number of pages | 9 |
| Journal | Expert Opinion on Drug Discovery |
| Volume | 8 |
| Issue number | 11 |
| DOIs | |
| State | Published - 1 Nov 2013 |
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Keywords
- Antiviral agent
- Boceprevir
- NS3 protease
- Peptidomimetic
- Protease inhibitor
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The discovery and development of boceprevir. / Rotella, David P.
In: Expert Opinion on Drug Discovery, Vol. 8, No. 11, 01.11.2013, p. 1439-1447.Research output: Contribution to journal › Review article
TY - JOUR
T1 - The discovery and development of boceprevir
AU - Rotella, David P.
PY - 2013/11/1
Y1 - 2013/11/1
N2 - Introduction: Boceprevir was the first direct acting agent developed for the treatment of hepatitis C virus infection. Boceprevir functions by targeting NS3 protease, a viral enzyme essential for replication. This peptidomimetic molecule was optimized from a peptide lead to provide a potent, selective and orally bioavailable drug that can be combined with ribavirin and peg interferon to achieve sustained viral response (undetectable HCV RNA levels for 24 weeks after completion of therapy) in patients infected with Genotype 1 of the virus. Areas covered: This article provides a review of the pre-clinical and clinical discovery of boceprevir. This review includes the role and function of its molecular target, NS3 protease, as well as the assays used to measure in vitro efficacy, compound optimization and clinical studies to demonstrate safety and efficacy. Expert opinion: As the first direct acting anti-HCV agent, boceprevir represents an important advance in therapy of this widespread chronic disease. Yet, while this therapy is a valuable approach, it does have limitations. Studies have suggested that 30% of patients do not achieve sustained viral response and 11% of patients have developed anemia and/or neutropenia. Current drug discovery and development efforts are underway to develop novel therapeutic options that address these issues.
AB - Introduction: Boceprevir was the first direct acting agent developed for the treatment of hepatitis C virus infection. Boceprevir functions by targeting NS3 protease, a viral enzyme essential for replication. This peptidomimetic molecule was optimized from a peptide lead to provide a potent, selective and orally bioavailable drug that can be combined with ribavirin and peg interferon to achieve sustained viral response (undetectable HCV RNA levels for 24 weeks after completion of therapy) in patients infected with Genotype 1 of the virus. Areas covered: This article provides a review of the pre-clinical and clinical discovery of boceprevir. This review includes the role and function of its molecular target, NS3 protease, as well as the assays used to measure in vitro efficacy, compound optimization and clinical studies to demonstrate safety and efficacy. Expert opinion: As the first direct acting anti-HCV agent, boceprevir represents an important advance in therapy of this widespread chronic disease. Yet, while this therapy is a valuable approach, it does have limitations. Studies have suggested that 30% of patients do not achieve sustained viral response and 11% of patients have developed anemia and/or neutropenia. Current drug discovery and development efforts are underway to develop novel therapeutic options that address these issues.
KW - Antiviral agent
KW - Boceprevir
KW - NS3 protease
KW - Peptidomimetic
KW - Protease inhibitor
UR - http://www.scopus.com/inward/record.url?scp=84886602795&partnerID=8YFLogxK
U2 - 10.1517/17460441.2013.843525
DO - 10.1517/17460441.2013.843525
M3 - Review article
C2 - 24079543
AN - SCOPUS:84886602795
VL - 8
SP - 1439
EP - 1447
JO - Expert Opinion on Drug Discovery
JF - Expert Opinion on Drug Discovery
SN - 1746-0441
IS - 11
ER -