In human cells, specific proteins can be enzymatically linked to a palmitic acid molecule in a process called palmitoylation. It is well understood that palmitoylation can activate proteins responsible for cancer progression (such as HRas and NRas), but there are no available therapies to inhibit this process.
At Palm Therapeutics, we are leveraging our proprietary technology to develop small molecule depalmitoylating drugs (DPALMs). DPALMs directly cleave palmitoyl groups from target proteins and inhibit their function. We have generated DPALM-based inhibitors for HRas and NRas, oncogenic targets long thought to be undruggable. These compounds shutdown oncogenic signaling pathways and trigger cancer cell death.
Melanoma affects nearly 200,000 Americans each year. When detected early, melanoma can usually be treated surgically, but once metastasized, few treatment options exist. The most aggressive form of the disease is driven by a mutation in the palmitoylated protein NRas. We are developing DPALMs which depalmitoylate NRas and selectively kill NRas-driven cancer cells. The DPALM approach has the potential to significantly improve outcomes in patients with melanoma as well as other cancers with high rates of NRas or HRas mutations such as HNSCC, AML, and Bladder Cancer.
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