AQX‐1125, small molecule SHIP1 activator inhibits bleomycin‐induced pulmonary fibrosis
Bibliographic record
Abstract
Background and Purpose The phosphatase SHIP1 negatively regulates the PI3K pathway, and its predominant expression within cells of the haematopoietic compartment makes SHIP1 activation a novel strategy to limit inflammatory signalling generated through PI3K. AQX‐1125 is the only clinical‐stage, orally administered, SHIP1 activator. Here, we demonstrate the prophylactic and therapeutic effects of AQX‐1125, in a mouse model of bleomycin‐induced lung fibrosis. Experimental Approach For prophylactic evaluation, AQX‐1125 (3, 10 or 30 mg·kg−1·d−1, p.o.) or dexamethasone (1 mg·kg−1·d−1, i.p.) were given to CD‐1 mice starting 3 days before intratracheal administration of bleomycin (0.1 IU per mouse) and continued daily for 7 or 21 days. Therapeutic potentials of AQX‐1125 (3, 10 or 30 mg·kg−1·d−1, p.o.) or pirfenidone (90 mg·kg−1·d−1, p.o.) were assessed by initiating treatment 13 days after bleomycin instillation and continuing until day 28. Key Results Given prophylactically, AQX‐1125 (10 and 30 mg·kg−1) reduced histopathological changes in lungs, 7 and 21 days following bleomycin‐induced injury. At the same doses, AQX‐1125 reduced the number of total leukocytes, neutrophil activity, TGF‐β immunoreactivity and soluble collagen in lungs. Administered therapeutically, AQX‐1125 (10 and 30 mg·kg−1) improved lung histopathology, cellular infiltration and reduced lung collagen content. At 30 mg·kg−1, the effects of AQX‐1125 were similar to those of pirfenidone (90 mg·kg−1) with corresponding improvements in disease severity. Conclusions and Implications AQX‐1125 prevented bleomycin‐induced lung injury during the inflammatory and fibrotic phases. AQX‐1125, given therapeutically, modified disease progression and improved survival, as effectively as pirfenidone.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.002 | 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 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".