{"entity":{"id":"alc1","kind":"target","name":"ALC1 (CHD1L)","aka":["ALC1","amplified in liver cancer 1","chromodomain helicase DNA binding protein 1 like"],"tldr":"ALC1 loosens packed DNA at sites of damage so it can be repaired. Cancers that already lack the BRCA repair route, such as some breast and ovarian cancers, lean on it, and losing it made such cells far more sensitive to PARP inhibitors in the laboratory; an ALC1 inhibitor is in early trials.","summary":"CHD1L, known as ALC1 (chromosome 1q21.1), is an ATP-dependent chromatin remodeller recruited to DNA damage through poly(ADP-ribose); it slides nucleosomes away from DNA breaks and helps remove PARP2 from chromatin (UniProt Q86WJ1). A CRISPR screen published in Nature Cell Biology in 2021 identified ALC1 as a key determinant of PARP inhibitor toxicity in homologous recombination-deficient cells: its loss reduced the viability of BRCA-mutant cells and raised their sensitivity to PARP inhibitors by up to 250-fold while overcoming several resistance mechanisms (Verma et al.,doi:10.1038/s41556-020-00624-3). In OnCo, EIS-12656 is an oral, brain-penetrant allosteric ALC1 inhibitor in a phase 1 trial including breast and ovarian cancer.","asOf":"2026-11-03","links":[{"label":"HGNC HGNC:1916","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1916"},{"label":"UniProt Q86WJ1","url":"https://www.uniprot.org/uniprotkb/Q86WJ1/entry"},{"label":"NCBI Gene 9557","url":"https://www.ncbi.nlm.nih.gov/gene/9557"},{"label":"ALC1 links chromatin accessibility to PARP inhibitor response in homologous recombination-deficient cells (Nat Cell Biol 2021)","url":"https://doi.org/10.1038/s41556-020-00624-3"}],"tags":["pipeline-gap-target"],"related":["parp"],"cancers":["breast-cancer","ovarian"],"sections":[],"technologies":[],"targets":[],"drugs":["eis-12656"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Prevalence not recorded: HGNC, UniProt and the paper cited give no positivity rate."],"provenance":{"editedBy":"OnCo gap audit, class 5 targets (HGNC REST, UniProt REST, Europe PMC, corpus drug records)","editedOn":"2026-11-03"},"symbol":"CHD1L","role":["drug-target"],"sources":[],"specificitySources":[],"hgnc":"HGNC:1916","ensembl":"ENSG00000131778","uniprot":"Q86WJ1","entrez":"9557","biology":"ATP-dependent chromatin remodeller whose activity is switched on by binding histones that carry poly(ADP-ribose) at DNA lesions (UniProt Q86WJ1).","whereFound":["Homologous recombination-deficient cancers, including BRCA-mutant breast and ovarian cancer (doi:10.1038/s41556-020-00624-3)","Breast and ovarian cancer (EIS-12656 trial)"],"targetClass":"enzyme","prevalence":[]},"route":"/targets/alc1/","neighbours":{"target":[{"id":"parp","kind":"target","name":"PARP","route":"/targets/parp/"}],"cancer":[{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"}],"drug":[{"id":"eis-12656","kind":"drug","name":"EIS-12656","route":"/drugs/eis-12656/"}]}}