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ALC1 inhibitor EIS-12656

An orally bioavailable allosteric inhibitor of the chromatin remodeling enzyme chromodomain-helicase-DNA-binding protein 1-like (CHD1L; amplified in liver cancer 1; ALC1), with potential antineoplastic activity. Upon oral administration, ALC1 inhibitor EIS-12656 selectively targets, allosterically binds to and inhibits the activity of ALC1, thereby preventing ALC1/poly(ADP-ribose) polymerase (PARP)-mediated repair of DNA breaks in tumor cells. This enhances the accumulation of DNA strand breaks and promotes genomic instability eventually leading to apoptosis. This inhibits tumor cell proliferation and may enhance the cytotoxicity of PARP inhibitors and DNA-damaging agents. ALC1, a SNF2 family ATPase that modulates the DNA retention of PARPs and other DNA repair enzymes, plays an important role in DNA damage repair. It is overexpressed in cancer cells with homologous recombination deficient (HRD) mutations. EIS-12656 is able to cross the blood-brain barrier (BBB).
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Code name:EIS 12656
EIS-12656
EIS12656
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