AI identifies (Z)-endoxifen as a potential therapeutic candidate for glioblastoma
Insilico Medicine and Atossa Therapeutics have published a joint study in Nature Scientific Reports pointing to (Z)-endoxifen as a promising candidate for glioblastoma multiforme (GBM). The work represents a large-scale, AI-guided repurposing effort that scored GBM highly among hundreds of oncology indications for further investigation.
GBM remains one of the most aggressive primary brain tumors in adults, with a five-year survival rate of roughly 4%. The study combines multi-omics modeling with wet-lab validation to probe whether endoxifen-an active metabolite of tamoxifen with known activity in endocrine-resistant breast cancer-can counter key GBM programs.
Why GBM rose to the top
Using Insilico's PandaOmics platform, researchers screened more than 900 cancer indications against weighted transcriptomic signatures from endoxifen-treated datasets. The platform integrated multiple evidence streams and unmet-need scoring to rank opportunities.
- Differential expression and pathway enrichment
- Protein-protein interaction networks and mechanistic NLP
- Disease unmet-need modeling with survival context
GBM consistently ranked near the top, warranting mechanistic follow-up and experimental testing.
What the data shows
AI-driven analyses identified more than 1,400 shared genes between GBM tumors and endoxifen-treated cells, indicating strong reversal of tumor-promoting programs. Predicted effects aligned with suppression of unchecked proliferation, inflammation, metabolic dysregulation, and aggressive phenotypes.
Single-cell sequencing pinpointed malignant-cell genes associated with poorer survival and aggressive subtypes; these targets were downregulated by endoxifen. The signal converged on biology that matters clinically, not just expression noise.
Wet-lab validation
In vitro, (Z)-endoxifen significantly reduced GBM cell proliferation and induced apoptosis. It showed greater cytotoxic activity than high-dose temozolomide and produced enhanced effects in combination settings.
In vivo, endoxifen was well tolerated across tested doses. Together, the computational and experimental evidence supports advancing (Z)-endoxifen as a GBM candidate for further preclinical and clinical study.
What leaders said
"This collaboration with Insilico Medicine provides a whole new indication in which we might explore the utility of endoxifen, and potentially significant new opportunities to address an extremely underserved set of cancer patients," said Steven Quay, M.D., Ph.D., CEO of Atossa Therapeutics. He noted that while much of their work centers on women's health, these findings extend into GBM and other high-ranking indications, including Duchenne muscular dystrophy and multiple gynecologic cancers.
"Atossa is deeply committed to scientific leadership in the prevention and treatment of high risk breast cancers, and Insilico is honored to collaborate with the company to advance genuine innovation and expand indications across different areas of oncology," said Alex Zhavoronkov, Ph.D., Founder and CEO of Insilico Medicine. He added that the joint research program includes additional studies that remain unpublished.
For researchers and translational teams
- Repurposing opportunity: An extensively characterized molecule with human safety data may shorten early development timelines if efficacy signals hold.
- Mechanism-led ranking: Cross-referencing treatment signatures with tumor biology can surface tractable programs beyond hormone signaling alone.
- Single-cell resolution: Targeting malignant-cell states linked to poor outcomes strengthens rationale for follow-up in defined GBM subtypes.
- Combination logic: Additive or synergistic effects with temozolomide deserve structured exploration in preclinical models and, if warranted, early trials.
Methods snapshot
- Indication screen: >900 oncology indications prioritized via PandaOmics
- Evidence: Differential expression, pathway enrichment, PPI networks, mechanistic NLP, unmet-need modeling
- Granularity: Tumor bulk data integrated with single-cell datasets
- Validation: In vitro cytotoxicity and apoptosis; in vivo tolerability
Platform performance context
From 2021 to 2024, Insilico nominated 20 preclinical candidates, averaging 12-18 months from project start to preclinical candidate nomination. Each program synthesized and tested approximately 60-200 molecules, indicating a leaner path through early discovery.
About Insilico Medicine
Insilico Medicine is a global AI-driven biotech company combining its Pharma.AI platform with automated laboratory capabilities to accelerate discovery across fibrosis, oncology, immunology, pain, and metabolic diseases. The company also applies its platform to adjacent domains, including advanced materials and agriculture. More at insilico.com.
About Atossa Therapeutics
Atossa Therapeutics (Nasdaq: ATOS) is a clinical-stage biopharmaceutical company developing therapies for high unmet needs in breast cancer. The company focuses on programs and data packages that can support future regulatory submissions and potential commercialization. Details at atossatherapeutics.com.
Background on GBM is available from the National Cancer Institute: NCI glioblastoma overview.
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