Recent advance in macrocyclic CDK inhibitors
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Cyclin-dependent kinases (CDKs) are central regulators of the cell cycle progression and transcription, making them attractive targets especially in oncology. The clinical success of CDK4/6 inhibitors in hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer has highlighted the therapeutic potential of CDK inhibition, along with ongoing clinical evaluation of other CDK-targeted agents. Despite the progress, challenges still remain due to off-target toxicity and the emergence of resistance. Recently, macrocycle-based drug design has gained recognition for its ability to enhance the kinase inhibitory activities and selectivity, improve drug-like properties, and potentially overcome resistance. This review summarizes recent advances (2015-2025) in macrocyclization strategies for CDK inhibitors, tracing the structural modification process from the acyclic scaffolds and highlighting their potential to address key limitations of current therapies.
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.
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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) | 0.000 | 0.000 |
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 it