This invention relates to the use of
small molecule compounds that allosterically inhibit ALC1 (CHD1L), particularly two classes of ALC1 (CHD1L) allosteric inhibitors of formulas (I) and (II). When combined with inhibitors of several classes of
cancer drugs, namely
topoisomerase I,
topoisomerase II, ATM, ATR, Wee1, BRD, and MEK, or when combined with
mitomycin C,
paclitaxel,
ionizing radiation, or
antibody-
drug conjugates having tumor-specific antibodies conjugated to TOP1 inhibitors, the
small molecule compounds and the allosteric inhibitors exhibit enhancing, preferably additive, effects in the treatment of proliferative diseases. Furthermore, this invention relates to the ALC1 inhibitor of formula (II), which, when combined with PARP inhibitors (poly(ADP-
ribose)-
polymerase inhibitors (PARPi)), exhibit synergistic effects in the treatment of
pancreatic cancer or
fallopian tube cancer. By synergizing with the functions of the aforementioned
cancer drugs, the ALC1 inhibitors, particularly those of formulas (I) and (II) that enhance the
cancer cell killing properties of the aforementioned
cancer drugs, are particularly capable of achieving treatments in which any of the aforementioned inhibitors have already been used as part of standard care.