Breaking: MIT Chemists Synthesize Verticillin A After 50-Year Quest, Flag Promising Lab Results for Pediatric Brain Cancer
Cambridge, MA – In a landmark breakthrough, researchers at the Massachusetts Institute of Technology have finaly synthesized verticillin A, a highly intricate fungal molecule long eyed for its anticancer potential. The development marks the first times scientists have produced this compound in more than five decades, unlocking the ability to create variants for further study.
The journey to verticillin A’s lab production has been arduous. Discovered in 1970 from a fungus that uses the molecule as a natural defense, verticillin A drew attention for its noted anticancer and antimicrobial activities. Yet its extreme structural complexity-comprising 10 rings and eight stereogenic centers-made synthetic production exceedingly difficult until now.
A key insight from the research team, led by MIT chemists, is that a small difference matters immensely: verticillin A differs from a closely related compound synthesized in 2009 by onyl two oxygen atoms. Those extra atoms render the molecule far more fragile during chemical reactions, complicating attempts to build it step by step in the lab.
To overcome these hurdles, the team overhauled the synthesis strategy. Beginning with a beta-hydroxytryptophan derivative, they reoriented the sequence of bond formations and exercised strict stereochemical control at every step. The process required 16 synthesis steps in total, culminating in a laboratory-ready verticillin A-a breakthrough for modern synthetic chemistry.
With the molecule now accessible, researchers have begun exploring derivatives.A collaboration with the Dana-Farber Cancer Institute involved testing these compounds on human cancer cells. Notably, some verticillin A derivatives demonstrated activity in diffuse midline glioma (DMG) cells that express high levels of the EZHIP protein, which influences DNA methylation. In these cells,certain derivatives significantly increased DNA methylation and triggered cancer cell death.
“Natural products themselves aren’t necessarily the most potent agents, but the ability to synthesize them enables the creation of more stable and effective derivatives,” the study leader explained. The work emphasizes that pinpointing molecular targets is crucial for developing a new generation of more precise cancer therapies.
despite the encouraging findings, officials stress that verticillin A is not yet ready for clinical use. Additional testing-including animal-model studies-will be needed to ensure safety and effectiveness before any human trials. The researchers caution that this remains early-stage science, with revelation and optimization far from clinical application.
The project consolidates a cross-disciplinary effort spanning chemistry, chemical biology, and cancer biology, underscoring how synthetic access to complex natural products can drive therapeutic innovation. The team also notes that they have profiled their leading compounds across more than 800 cancer cell lines to broaden understanding of their potential activity in other cancers.
Funding for the work came from the National Institute of General Medical Sciences,the Ependymoma Research Foundation,and the Curing Kids Cancer Foundation. The researchers cited continued support as essential to advancing preclinical evaluation and future clinical exploration. NIGMS, Ependymoma Research Foundation, and Curing Kids Cancer Foundation are among the funders cited in related releases. For the latest context,see ScienceDaily coverage and institutional updates from MIT.
Key facts at a glance
| Key Fact | Details |
|---|---|
| Discovery of verticillin A | Identified in 1970 from a fungus |
| Primary breakthrough | First synthetic production achieved by MIT researchers after decades of effort |
| Structural complexity | 10 rings and eight stereogenic centers |
| Difference from similar compound | Two additional oxygen atoms complicate synthesis and increase fragility |
| Number of synthesis steps | 16 steps to obtain verticillin A in the lab |
| Early therapeutic signal | Derivatives show activity in DMG cells with EZHIP-linked methylation changes |
| Clinical status | Preclinical; no clinical use yet |
| Funding | National Institute of General Medical Sciences; Ependymoma Research Foundation; Curing Kids Cancer Foundation |
Disclaimer: This report covers early-stage, laboratory findings. Results in cells and test tubes do not guarantee safety or effectiveness in humans. Clinical applications, if any, will require extensive preclinical and regulatory review.
As researchers pursue further validation in animal models and other preclinical studies, the scientific community will watch closely how these verticillin A derivatives behave across different cancer types. The potential to harness a natural product through synthetic chemistry underscores a broader trend in drug discovery: making elusive molecules accessible to design safer and more effective therapies.
What do you think could be the most impactful cancer types to explore with verticillin A derivatives next?
Would you support continued funding for synthetic chemistry programs aimed at unlocking natural products with potential anticancer properties?
For readers seeking more depth, reference materials and related discussions are available from institutional sources and coverage by major science outlets.
