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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.
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.
In plain words · 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.
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.
ATP-dependent chromatin remodeller whose activity is switched on by binding histones that carry poly(ADP-ribose) at DNA lesions (UniProt Q86WJ1).
1 product aims at ALC1 (CHD1L): small molecules. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
ATP-dependent chromatin remodeller whose activity is switched on by binding histones that carry poly(ADP-ribose) at DNA lesions (UniProt Q86WJ1).
EIS-12656 is an experimental small molecule from Eisbach Bio, in phase 1 trials for homologous recombination deficient advanced solid tumours, breast cancer and ovarian cancer.
Query for this target: (TITLE:"ALC1" OR ABSTRACT:"ALC1" OR TITLE:"CHD1L" OR ABSTRACT:"CHD1L" OR TITLE:"amplified in liver cancer 1" OR ABSTRACT:"amplified in liver cancer 1" OR TITLE:"chromodomain helicase DNA binding protein 1 like" OR ABSTRACT:"chromodomain helicase DNA binding protein 1 like") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about ALC1 (CHD1L), not a curated reading list.
Shares PARP and the tag pipeline-gap-target.
Shares Ovarian cancer and the tag pipeline-gap-target.
Shares Breast cancer (all types) and the tag pipeline-gap-target.
Shares PARP, Ovarian cancer, Breast cancer (all types).
Shares PARP, Ovarian cancer, Breast cancer (all types).
Shares PARP, Breast cancer (all types).
Shares PARP, Breast cancer (all types).
Shares PARP, Ovarian cancer, Breast cancer (all types).
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