TMC-435, an NS3/4A protease inhibitor for the treatment of HCV infection.
Bibliographic record
Abstract
TMC-435, being developed by Tibotec Pharmaceuticals Ltd, is an orally administered, macrocyclic inhibitor of the HCV NS3/4A serine protease. HCV infection can cause chronic hepatitis, cirrhosis of the liver and hepatocellular carcinoma. The HCV NS3/4A enzyme is an essential component for viral replication, suggesting that this protein is a key therapeutic target. Biochemical assays demonstrated potent inhibition of HCV NS3/4A by TMC-435 in all HCV genotypes tested, with the exception of HCV-3. In cellular replicon models, the compound selectively inhibited HCV-1 replication and displayed additive effects with ribavirin, and had synergistic activity with IFNalpha and an NS5B polymerase inhibitor. Pharmacokinetic data demonstrated high exposure and good oral bioavailability, supporting once-daily dosing of TMC-435 in humans. In phase I and II clinical trials, the administration of TCM-435 to patients infected with HCV-1, alone or in combination with PEG-IFNalpha and ribavirin, produced significant reductions in HCV-RNA without any significant adverse effects, thus providing a basis for further development of this compound as an anti-HCV therapeutic agent. At the time of publication, phase II trials with TMC-435 were ongoing.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".