ccs

The metallo-protein Cu/Zn-superoxide dismutase (SOD1) is a ubiquitous enzyme responsible for scavenging superoxide radicals. Mutations in SOD1, which alter its metal binding capacity and can result in protein misfolding and aggregation, have been linked to familial amyotrophic lateral sclerosis (ALS). Cu-ATSM is an orally bioavailable, blood-brain barrier permeable complex that has traditionally been used in cellular imaging experiments to selectively label hypoxic tissue via its susceptibility to reduction by oxygen-depleted mitochondria. More recently, Cu-ATSM has been reported to improve locomotor function and survival in a transgenic ALS mouse model by delivering copper specifically to cells in the spinal cords of mice producing misfolded SOD1 proteins. Copper chaperone for SOD (CCS) is presumed to utilize the copper from Cu-ATSM to prevent misfolding of the SOD1 protein.

Inobrodib (CBP-IN-1) is a potent inhibitor of p300 CBP bromodomain.

DA-PROTAC is a potent degrader of the copper ion-transport proteins Atox1 and CCS, capable of binding to both proteins and facilitating their association with E3 ligase. This interaction enhances the ubiquitination and subsequent proteasomal degradation of Atox1 and CCS. DA-PROTAC is utilized in triple negative breast cancer research [1].

DC_AC50 is a dual inhibitor of Atox1 and CCS (copper chaperones), aimed at reducing or preventing acquired chemotherapy resistance by inhibiting intracellular copper chaperones. It binds to Atox1 and CCS, thereby reducing cancer cell proliferation and tumor growth.