STAT INHIBITORS
The Signal Transducer and Activator of Transcription (STAT) proteins are members of a family of transcription factors that regulate the expression of numerous critical genes involved in cell cycle, cell proliferation, migration, and survival. However, the constitutive activation of STAT3 and STAT5 is frequently detected in clinical samples from a wide range of human cancers. Targeted blocking of STAT3 is an attractive therapeutic approach for most types of human cancers, and ASC has developed a novel class of drug candidates, which target STAT3 and 5 and are potently suppressing a wide range of tumor cell lines growth in vitro and inhibiting tumor progression in vivo in xenograft tumor models, including human colon, prostate and non-small cell lung cancers.
Lead STAT Inhibitors are a novel class of compounds designated as the ASC-ST series of small molecule candidates. To date STAT inhibitor ASC-ST compounds have undergone extensive preclinical testing and achieved positive proof-of-concept data to support translational potential as chemopreventive or therapeutic agents in diverse forms of solid and hematological cancer. A comprehensive series of preclinical studies is underway to optimize efficacy, safety, and formulation for oral or parenteral delivery of this novel oncology platform.
The ASC-ST small molecule program represents the first series of lead compounds identified from a novel class of drug candidates intended for development into therapeutics for solid and hematological cancers. ASC ST compounds exhibit high preferential action and potently inhibit STAT3 and STAT5 activity. ASC-ST compounds inhibition of STAT3 and STAT5 has been tested in over 25 distinct human cancer cell lines in vitro and 3 human tumors (colon, prostate and non-small cell lung) xenograft in animal models. These studies demonstrate inhibition of STAT3 and STAT5 activity by ASC-ST results in growth arrest and decreased cancer cell viability through inducing apoptosis.
ASC’s STAT inhibitor program represents a cancer treatment platform of immense medical and commercial importance. To date the ASC’s STAT inhibitor compounds have produced positive proof of concept data to support clear translational potential as chemopreventive or therapeutic agents in a diverse number of solid and hematological cancers. A comprehensive series of studies is underway to optimize efficacy, safety, and formulation for oral or parenteral delivery.
ASC CLINICAL BENEFITS
STAT INHIBITOR PROGRAMS: ASC-ST (FOR SOLID TUMOR AND HEMATOLOGICAL CANCERS)
Novel First in Class Mechanism of Action, Wide Pharmacological Applications
- Achieves greater efficacy through:
- Targeting a validated oncogenic protein constitutively activated in a wide range of human cancers
- ASC-ST compounds demonstrate striking potency in suppressing malignant transformation, reduce cancer cell growth and invasion, and induce cellular apoptosis to cause cancer cell death
- Superior to “kinase inhibitor”-based cancer treatment strategies, such as multi-functional JAK kinases and other mediators of STAT activity
- Selective inhibition of STAT proteins eliminates malignant transformation and cancer cell growth while maintaining normal upstream kinase activity essential for healthy cellular function
- Elevated STAT3 and STAT5 activity is largely confined to cancerous cells, with healthy cells exhibiting significant lower levels (except under inflammatory reactions) – allows for favorable safety profile.
|