Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) have published a study in Nature Communications shedding new light on how K-80003 (TX803), an anti-cancer agent discovered at the Institute, prevents activation of the PI3K pathway, resulting in inhibition of cancer cell growth. Because the PI3K pathway is common to many cancers, K-80003 could have broad therapeutic applications. Tarrex Biopharma, Inc. has licensed the compound and announced they will soon begin Phase 1 clinical trials at the Dana Farber Cancer Center for patients with colorectal cancer.
Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) have published a study in Nature Communications shedding new light on how K-80003 (TX803), an anti-cancer agent discovered at the Institute, prevents activation of the PI3K pathway, resulting in inhibition of cancer cell growth. Because the PI3K pathway is common to many cancers, K-80003 could have broad therapeutic applications. Tarrex Biopharma, Inc. has licensed the compound and announced they will soon begin Phase 1 clinical trials at the Dana Farber Cancer Center for patients with colorectal cancer.
“K-80003 binds specifically to a truncated form of the retinoid X receptor-alpha (tRXRα) protein that promotes tumors,” says Xaio-kun Zhang, Ph.D., adjunct professor and senior author of the paper. “When it binds tRXRα, it freezes the protein into an inactive (tetrameric) configuration that prevents it from stimulating the PI3K pathway.
“A major goal of this study was to dig deeper and find out why this compound is so effective, and appears to have so few side effects,” adds Zhang. “We wanted to visualize how tRXRα and K-80003 physically interact—at atomic resolution—in a way that makes this such a promising cancer drug.”
Working with the lab of Robert Liddington, Ph.D., professor at SBP, the research team used X-ray crystallography to find that six molecules of K-80003 bound to the tetramer interfaces.
Read more at Sanford Burnham Prebys Medical Discovery Institute
Image: Xaio-kun Zhang, Ph.D., is an adjunct professor at Sanford Burnham Prebys Medical Discovery Institute. Dr. Zhang studies how vitamin A and its analogs treat and prevent various cancers. (Credit: Sanford Burnham Prebys Medical Discovery Institute)
