Preclinical development of Aneustat (OMN54): a multifunctional multi-targeted natural product derivative with anti-tumor, anti-inflammatory and immuno-modulatory activity
Bibliographic record
Abstract
C67 Aneustat (OMN54), a natural product derivative, has anti-tumor, anti-inflammatory and immuno-modulatory activity as a single agent and in combination with standard of care cytotoxic agents. OMN54 was formulated to inhibit multiple signaling pathways demonstrated to be altered in cancer and to modulate immune responses. It is now appreciated that cancer development is exquisitely susceptible to regulation by immune cells. OMN54 is in late stage pre-clinical development. In vitro studies using microarrays and QRT-PCR determined genomic targets of OMN54, which include genes involved in apoptosis (Bax), adhesion (FN-1), metastases (CD26), angiogenesis (HIF1I±) , inflammation (PTGS 1, 2) as well as tumor specific genes (KLK3). Analysis of 25 cytokines chemokines and growth factors using the Luminex platform demonstrated potent immunomodulatory activity of OMN54 treated peripheral blood mononuclear cells in the presence of mitogen but no effect on normal cytokine production in the absence of mitogen. In vivo, OMN54 significantly inhibited growth of DU145 (androgen-independent) human prostate cancer tumors and induced apoptosis in chemo-resistant AB79 human small cell lung cancer in xenograft studies in mice. OMN54 was shown by flow cytometry to enhance the cycling of AB117 non-small cell lung cancer cells (i.e. entry into G1 from G0 of the cell cycle). Non-small cell lung cancer tumors treated with OMN54 show an increase in the percentage of S, G2 and M cells from about 30% to 50% (cells in these stages are most responsive to cytotoxic agents). As such Aneustat could be a powerful adjuvant to either chemotherapy or to radiation therapy based upon its action on enhanced cell cycling. A three-week treatment with OMN54 imparts significantly increased survival on A549 tumor bearing mice over a 3 month period compared to control treated A549 tumor bearing mice. OMN54 also demonstrated additive or synergistic activity in combination with a number of standard-of-care cytotoxics, including gemcitabine, pemetrexed and methotrexate. OMN54 was well-tolerated in IND-enabling toxicology studies that included multi-day oral dosing in rats over a two, four and six month time period.â\#8364; In summary, OMN54 is effective in inhibiting multiple targets and pathways controlling tumor growth in a number of model systems. IND-enabling toxicology studies have demonstrated OMN54 is orally bioavailable with no visible toxicity at therapeutic doses. A phase I clinical trial in cancer patients was approved in October 2006.
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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 | 0.000 | 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 | 0.000 |
| 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".