Experimental drug forces cancer cells to overconsume sugar while blocking fat metabolism

Researchers at the University of Texas at Austin have developed an experimental compound that simultaneously accelerates sugar metabolism and blocks fat metabolism in cancer cells, according to a study published in Nature Chemical Biology. The molecule, designated XJ-4-85, binds to the enzyme PFKL at two sites, increasing the rate of glycolysis, and then releases a payload that inhibits CPT2, an enzyme required for fatty acid oxidation.

In laboratory tests, the drug was effective against human melanoma, leukemia, breast, lung, liver, and neuroblastoma cell lines. In mice implanted with an aggressive form of melanoma, most cancer cells died while noncancerous cells were much less affected, the researchers reported.

The strategy differs from conventional metabolic inhibitors that aim to starve tumors of glucose. Instead, the new compound drives cancer cells into metabolic overdrive while cutting off their backup energy source, creating lethal stress. Co-corresponding author Xiaolu (Lulu) Lim Ang Cambronne described the mechanism as a "two-headed dragon" that puts one cellular process into overdrive while weakening another.

The researchers positioned the compound as a fully chemical alternative to antibody-drug conjugates (ADCs), which use large antibodies to deliver chemotherapy payloads. Because the new molecule is smaller, it can target intracellular proteins such as PFKL and CPT2, and it is easier to manufacture than antibody-based therapies, said co-corresponding author Ken Hsu, an associate professor of chemistry.

Postdoctoral fellow Xiaoding Jiang, who designed the molecule, said the dual mechanism was unexpected and required extensive molecular characterization to understand. The team also noted the compound's selective binding to cancer cells over healthy cells as a surprising finding.

The authors emphasized that the research remains in early stages and that substantial additional laboratory testing is required before human studies could begin. They also introduced the broader concept of "electrophile-drug conjugates" (EDCs) as a modular platform that could be adapted for diseases beyond cancer.

The work involved collaboration across multiple departments at UT Austin and with researchers at the University of Washington. The study was published in Nature Chemical Biology with DOI 10.1038/s41589-026-02289-9.