Rigel study shows potential for UHRF1 as cancer target

By Angela McDaniels

Seattle, Nov. 28 - Rigel Pharmaceuticals Inc. said its study findings show the potential of UHRF1, an E3 ubiquitin ligase, as an attractive oncology target.

Early cellular events associated with tumor formation often include loss of cell-cycle checkpoints or alteration in growth-signaling pathways. Identification of novel genes involved in the regulation of cellular proliferation and cellular repair may lead to new classes of cancer therapeutics, the company said.

Scientists at Rigel, in collaboration with Johnson & Johnson Pharmaceutical Research and Development, found that UHRF1 expression is elevated in proliferating cells and primary tumors.

The scientists further found that interference with UHRF1 ubiquitin ligase function rendered cells sensitive to the effects of chemotherapeutics, identifying a role for UHRF1 ligase activity in cellular survival, the company said.

"We are particularly interested in the selective inhibition of ubiquitin ligases, since it could lead to pharmaceutical product candidates with higher specificity and lower toxicity for cancer patients," executive vice president and chief scientific officer Donald G. Payan said in a company news release.

"The targeting of intracellular protein degradation pathways has become an especially attractive therapeutic strategy due to the success of proteasome inhibitors in the treatment of multiple myeloma."

The study findings were published in Molecular Biology of the Cell, the journal of the American Society for Cell Biology.

The study is part of a collaboration between Rigel and Johnson & Johnson to identify and validate novel drug targets that regulate the cell cycle and cancer progression.

Rigel is a drug development company based in South San Francisco, Calif., that discovers and develops small molecule drugs for the treatment of inflammatory diseases, cancer and viral diseases.

Based in New Brunswick, N.J., Johnson & Johnson is manufacturer of health care products for the consumer, pharmaceutical, medical devices and diagnostics markets.

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