ALC1 inhibitors for use in cancer treatment by enhancing the effects of several approved classes of cancer drugs

Abstract

The present invention relates to the use of small molecule compounds that allosterically inhibit ALC1 (CHD1L), in particular two classes of allosteric ALC1 (CHD1L) inhibitors, of Formula (I) and Formula (II), which exhibit a potentiating, preferably additive, effect in the treatment of proliferative diseases when combined with various classes of anticancer drugs, namely Topoisomerase I, Topoisomerase II, ATM, ATR, Wee1, BRD and MEK inhibitors, or when combined with mitomycin C, paclitaxel, ionizing radiation, or an antibody-drug conjugate with a tumor-specific antibody conjugated to a TOP1 inhibitor. Furthermore, the present invention relates to said ALC1 inhibitors of Formula (II) that show a synergistic effect in the treatment of pancreatic cancer or fallopian tube cancer when combined with a PARP inhibitor (poly(ADP-ribose) polymerase inhibitor (PARPi)).By being synergistic with the function of said anti-cancer drugs, said ALC1 inhibitors, in particular those of Formula (I) and Formula (II), enhance the cancer cell-destroying properties of the aforementioned anti-cancer drugs, enabling in particular therapeutic approaches where any of the aforementioned inhibitors are already used as part of standard treatment.