20240033363. ALC1 Inhibitors and Synergy with PARPi simplified abstract (Eisbach Bio GmbH)
Contents
ALC1 Inhibitors and Synergy with PARPi
Organization Name
Inventor(s)
William M. Menzer of München (DE)
Gunnar Knobloch of Planegg (DE)
Corinna Lieleg of Garching (DE)
Adrian Schomburg of Gräfelfing (DE)
Andreas Ladurner of Gräfelfing (DE)
Peter Sennhenn of München (DE)
ALC1 Inhibitors and Synergy with PARPi - A simplified explanation of the abstract
This abstract first appeared for US patent application 20240033363 titled 'ALC1 Inhibitors and Synergy with PARPi
Simplified Explanation
The present invention is about small molecule compounds that inhibit the alc1 enzyme and trap parp1, parp2, and/or parp3 on chromatin or at DNA damage sites. This disruption of alc1's chromatin remodeling forces allows for a highly selective therapy to target the DNA damage functions of parp enzymes in proliferative diseases, particularly BRCA-deficient cancers. The compounds engage in synthetic lethality between BRCA1/2 and alc1 by inhibiting the enzymatic activity. Additionally, by trapping parp enzymes, these inhibitors potentiate the cancer cell killing properties of parp inhibitors, overcome parp inhibitor resistance mechanisms, and provide an alternative approach to treating BRCA1/BRCA2 deficiency.
- Small molecule compounds inhibit alc1 and trap parp enzymes on chromatin or at DNA damage sites
- Disruption of alc1's chromatin remodeling forces enables selective therapy for targeting parp enzymes in proliferative diseases, especially BRCA-deficient cancers
- Compounds engage in synthetic lethality between BRCA1/2 and alc1 by inhibiting enzymatic activity
- Trapping parp enzymes enhances the cancer cell killing properties of parp inhibitors
- Enables overcoming parp inhibitor resistance mechanisms
- Alternative approach to treating BRCA1/BRCA2 deficiency
Potential Applications
- Treatment of BRCA-deficient cancers
- Therapy for proliferative diseases with altered DNA repair networks
Problems Solved
- Lack of selective therapy for targeting parp enzymes in proliferative diseases
- Parp inhibitor resistance mechanisms
Benefits
- Highly selective therapy for targeting DNA damage functions of parp enzymes
- Potentiation of cancer cell killing properties of parp inhibitors
- Alternative approach to treating BRCA1/BRCA2 deficiency
Original Abstract Submitted
the present invention relates to small molecule compounds that allosterically inhibit alc1 (chd1l) and which induce the trapping of parp1, parp2 and/or parp3 on chromatin or at dna damage sites. disruption of the chromatin remodeling forces of alc1 through these agents enables a highly selective therapy for targeting the dna damage functions of parp enzymes in several proliferative diseases, notably brca-deficient cancers. via inhibition of the enzymatic activity, the compounds engage the synthetic lethality between brca1/2 and alc1. by trapping parp enzymes, inhibitors of alc1 potentiate the cancer cell killing properties of parp inhibitors, enable therapeutic approaches where alc1 is amplified as an oncogene, therapeutically make it possible to overcome parp inhibitor resistance mechanisms and enable an alternative approach to the treatment of germline or acquired brca1/brca2 deficiency, including tumors defined by “brcaness” or other changes in dna repair networks.
