In Vitro Activity and Preclinical Profile of TMC435350, a Potent Hepatitis C Virus Protease Inhibitor
TMC435350 is a highly specific and potent inhibitor of NS3/4A protease selected from a series of novel macrocyclic inhibitors that has the potential for combination with other anti-HCV agents and the favorable pharmacokinetic profile.
Cathepsin K inhibitors prevent matrix-derived growth factor degradation by human osteoclasts.
- K. Fuller, K. Lawrence, T. Chambers
- BiologyBone
- 2008
Plasmepsins as potential targets for new antimalarial therapy
- K. Ersmark, B. Samuelsson, A. Hallberg
- Biology, MedicineMedicinal research reviews (Print)
- 1 September 2006
It seems clear that in order to achieve high‐antiparasitic activities in P. falciparum‐infected erythrocytes it is necessary to inhibit several of the haemoglobin‐degrading plasmepsins, which represent all classes which, to the best of the authors' knowledge, have been disclosed in journal articles to date.
Relationships between structure and interaction kinetics for HIV-1 protease inhibitors.
- P. Markgren, W. Schaal, U. Danielson
- Biology, ChemistryJournal of Medicinal Chemistry
- 25 October 2002
The interaction between HIV-1 protease and 58 structurally diverse transition-state analogue inhibitors has been analyzed by a surface plasmon resonance based biosensor and shows that different classes of inhibitors fall into distinct clusters in maps.
Discovery and development of simeprevir (TMC435), a HCV NS3/4A protease inhibitor.
- A. Rosenquist, B. Samuelsson, M. Beumont‐Mauviel
- Biology, MedicineJournal of Medicinal Chemistry
- 14 February 2014
The extensive medicinal chemistry effort to develop novel P2 cyclopentane macrocyclic inhibitors guided by HCV NS3 protease assays, the cellular replicon system, structure-based design, and a panel of DMPK assays are summarized.
Induced-fit binding of the macrocyclic noncovalent inhibitor TMC435 to its HCV NS3/NS4A protease target.
- M. Cummings, J. Lindberg, K. Simmen
- Chemistry, BiologyAngewandte Chemie
- 22 February 2010
The observed induced-fit binding of 1 to HCV NS3/NS4A protease, discuss key in vitro resistance mutations in the context of the complex, and disclose the new crystal structure for public analysis are analyzed.
Two-carbon-elongated HIV-1 protease inhibitors with a tertiary-alcohol-containing transition-state mimic.
- Xiongyu Wu, Per Ohrngren, M. Larhed
- ChemistryJournal of Medicinal Chemistry
- 24 January 2008
A new generation of HIV-1 protease inhibitors encompassing a tertiary-alcohol-based transition-state mimic has been developed. By elongation of the core structure of recently reported inhibitors with…
Structure-activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350.
- P. Raboisson, Herman A de Kock, K. Simmen
- Chemistry, BiologyBioorganic & Medicinal Chemistry Letters
- 1 September 2008
Potent inhibitors of the Plasmodium falciparum enzymes plasmepsin I and II devoid of cathepsin D inhibitory activity.
- K. Ersmark, I. Feierberg, A. Hallberg
- Biology, ChemistryJournal of Medicinal Chemistry
- 2004
To the best of the knowledge, these plasmepsin inhibitors represent the most selective reported to date and constitute promising lead compounds for further optimization.
Cyclic HIV-1 protease inhibitors derived from mannitol: synthesis, inhibitory potencies, and computational predictions of binding affinities.
- J. Hulten, N. M. Bonham, A. Hallberg
- Chemistry, BiologyJournal of Medicinal Chemistry
- 14 March 1997
Ten C2-symmetric cyclic urea and sulfamide derivatives synthesized from L-mannonic gamma-lactone and D-mannitol were selected to enable elucidation of the role of stereochemistry for binding affinity and to allow evaluation of the effects of variation in the link to the P1 and P1' phenyl groups on affinity.
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