Fra1 targeted SPEARs inhibit the interaction of cJun with Fra1 and disrupt AP-1 complex formation, thereby inhibiting oncogenic activity
Activator protein 1 (AP-1) is a transcription complex comprised of Jun and Fos protein subunits with involvement in a wide range of cellular processes, including proliferation, apoptosis and differentiation. Dysregulation of the AP-1 complex drives the expression of oncogenic factors such as cyclin D, E2F and DP1, and has been observed in head and neck, lung, breast, pancreatic, bladder, liver, melanoma and colorectal tumors, as well as many hematologic malignancies.
Fra1 program is currently in lead optimization
In preclinical studies to date, our Fra1 SPEAR candidate has demonstrated binding to Fra1 and cJun, disruption of the cJun/Fra1 AP-1 complex, and biologic activity both in vitro and in vivo.