About STAT3 (Signal Transducer and Activator of Transcription 3)
STAT3 is a transcription factor/signaling protein that is frequently activated in many forms of cancer.
STAT3 plays a crucial role in tumor cells as well as in the tumor microenvironment and is a highly promising target for cancer therapy. Direct STAT3 inhibitors have the potential to prevent metastasis, reverse drug resistance and induce apoptosis in cancer cells. Furthermore, STAT3 inhibitors have the potential to be combined with immunotherapies to increase response rates and efficacy, and with targeted drugs and chemotherapy to reverse and overcome treatment resistance in order to provide efficacious and safe cancer treatments.
STAT3 is an intractable drug target as it is an intracellular protein with no enzymatic activity and is activated by multiple upstream factors. Despite it not being a “classic drug target”, Glactone Pharma has developed a series of proprietary small molecules, based on the natural product galiellalactone (GPA500) as a lead, that act as STAT3 inhibitors. These small molecule STAT3 inhibitors bind directly to the DNA binding domain of STAT3, thereby inhibiting the function of the target.
Compared to antibodies and other biologics, small-molecule drugs offer several advantages:
- oral bioavailability allowing easier dosing
- greater exposure within the tumor microenvironment
- access to intracellular disease targets not tractable by protein therapeutic agents
- decreased risk of unmanageable systemic toxicities when combined with biologics.
Promising target in cancer
STAT3 is a very promising target in cancer due to its involvement in many key disease processes including proliferation, tumor induced immunosuppression, drug resistance and metastasis. STAT3 is an immunosuppressive oncogene pathway with pleiotropic carcinogenic effects. Aberrant STAT3 signaling is found both within tumor cells and in tumor-associated immune cells. A result of this is that STAT3 plays a pivotal role in the crosstalk between tumor cells and immune cells of the tumor microenvironment.
Glactone Pharma has built a strong proprietary portfolio of small-molecule STAT3 inhibitors based on the naturally occurring STAT3 inhibitor GPA500 (galiellalactone). The innovators behind Glactone Pharma have previously demonstrated that GPA500 binds directly to STAT3 and that this prevents the function of STAT3 regardless of up-stream activators.
Glactone Pharma is uniquely positioned to fulfill the promise of STAT3 as a drug target and bring new effective and safe therapies to patients and meet unfulfilled medical needs.