tcsc3723 ACTB-1003

ACTB-1003 is an oral kinase inhibitor with IC₅₀s of 6, 2 and 4 nM for FGFR1, VEGFR2 and Tie-2.

IC50 & Target: IC50: 6 nM (FGFR1), 2 nM (VEGFR2), 4 nM (Tie-2)^[1]

In Vitro: ACTB-1003 is an oral kinase inhibitor with multiple modes of action, targeting cancer mutations via FGFR inhibition FGFR1 (IC50=6 nM), angiogenesis through inhibition of VEGFR2 (2 nM), Tie-2 (4 nM), and induces apoptosis likely by targeting RSK (5 nM) and p70S6K (32 nM). ACTB-1003 is highly active with dose-dependent tumor growth inhibition in cell lines with FGFR genetic alterations - OPM2 human multiple myeloma and the murine leukemia Ba/F3-TEL-FGFR1. OPM2 cells harbor the FGFR3 t(4:14) translocation, FGFR3 K650E mutation and PTEN deletion while the Ba/F3-TEL-FGFR1 cells are driven by FGFR1 over-expression^[1].

In Vivo: ACTB-1003 is shown to inhibit tumor angiogenesis evident by the inhibition of CD31 staining in tumor sections. ACTB-1003 is combinable with 5-FU or paclitaxel without diminishing the activity or increasing the toxicity of these chemotherapy agents in the HCT-116 colon tumor xenograft model^[1].