Discovery of a Novel MNK Inhibitor (NSP-1047) with In Vivo Anti-acute Myeloid Leukemia Activity
Bibliographic record
Abstract
MAPK-interacting kinases (MNKs) phosphorylate the eukaryotic initiation factor 4E (eIF4E), critical for cap-dependent translation. The MNK/eIF4E pathway plays a role in the development and progression of various hematological and solid tumors. Here, we report the discovery of a novel polycyclic compound 21e (NSP-1047), which inhibits MNK1 and MNK2 with high potency, leading to a reduction in the phosphorylation of eIF4E. NSP-1047 shows strong in vitro antiproliferative activity against multiple acute myeloid leukemia (AML) cell lines. Meanwhile, it enhances anticancer immune responses by downregulating the expression of immune checkpoint proteins and suppressing the secretion of inflammatory cytokines. NSP-1047 displays excellent ADME and pharmacokinetic properties, and encouraging safety profiles, with a highest nonsevere toxic dose (HNSTD) of 750 and 200 mg/kg for SD rats and Beagle dogs, respectively. In vivo efficacy evaluation in AML xenografts demonstrates significant tumor suppression, with tumor regression observed at tolerated doses, both as monotherapy and in combination with Ara-C or venetoclax.
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 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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".