C19-9N is a potent, orally bioavailable pan-αv/α5β1 integrin antagonist, exhibits high affinity for αvβ3 (Kd=0.55 μM), αvβ5 (Kd=0.61 μM), α5β1 (Kd=0.88 μM), αvβ6 (Kd=0.41 μM) and αvβ8 (Kd=0.86 μM), blocks extracellular matrix (ECM)-integrin interaction.
C19-9N is a potent inhibitor of prostate cancer cell growth, migration, and invasion in vitro, significantly inhibits the proliferation of AR-positive CRPC (22RV1), AR-negative mCRPC (PC-3), and NEPC (NCI-H660) cells, with IC50 values of 0.49μM, 0.59μM, and 0.37μM, respectively.
C19-9N exerts multi-faceted anti-tumor effects through inducing apoptosis, arresting cell cycle progression, and suppressing integrin-mediated adhesion and migration.
C19-9N inhibits prostate cancer cell stemness and EMT process.
C19-9N significantly inhibits the expression of SRC and STAT3, as well as the phosphorylation of SRC, AKT, and STAT3, leading to downregulation of AR-FL/AR-V7 expression, blockade of their nuclear translocation, and suppression of AR transcriptional activity.
C19-9N (5 or 10 mg/kg, q.d.) dose-dependently suppresses tumor growth in mice bearing TRAMP-C1 xenografts, overcomes enzalutamide resistance in vivo.
C19-9N modulates tumor immune microenvironment by targeting TAMs and CD47 in resistant bone metastases.