Discovery of ART0380, a Potent and Selective ATR Kinase Inhibitor Undergoing Phase 2 Clinical Studies for the Treatment of Advanced or Metastatic Solid Cancers
Bibliographic record
Abstract
One of the hallmarks of cancer is high levels of DNA replication stress and defects in the DNA damage response (DDR) pathways, which are critical for maintaining genomic integrity. Ataxia telangiectasia and Rad3-related protein (ATR) is a key regulator of the DDR machinery and an attractive therapeutic target, with multiple ATR inhibitors holding significant promise in ongoing clinical studies. Herein, we describe the discovery and characterization of ART0380 ( 6 ), a potent and selective ATR inhibitor with a compelling in vitro and in vivo pharmacological profile currently undergoing Phase 2 clinical studies in patients with advanced or metastatic solid tumors as monotherapy and in combination with DNA-damaging agents (NCT04657068 and NCT05798611). ART0380 ( 6 ) has a favorable human PK profile suitable for both intermittent and continuous once-daily (QD) dosing, characterized by a dose-proportional increase in exposure and low variability.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".