Loading patent…
AssigneeThe Scripps Research Institute
InventorsBenjamin F. CRAVATT, Yongfeng TAO, Xiaoyu ZHANG, Dave REMILLARD, Ekaterina VINOGRADOVA, Minoru YOKOYAMA, Bruno MELILLO, Stuart SCHREIBER
Estimating the term…
Disclosed are bifunctional degraders comprising electrophilic PRO-TACs that engage DCAF1 and pharmaceutical compositions comprising the same. The bifunctional degraders are of Formula A-B-C wherein, A is a ligand to a protein of interest, B is a linker that is a bond or a chemical linker that is chemically linked to A and C, and C is a ligand to the E3 ligase substrate receptor DCAF1, wherein the protein of interest is any protein having a ligand that can form a covalent bond with the linker B; and C comprises an azetidinyl acrylamide that forms a covalent bond with C1113 of DCAF1 through a Michael addition reaction.
A bifunctional degrader of Formula (I)
A DCAF1 protein-probe adduct, wherein the probe binds to cysteine residue C1113 of DCAF1, wherein the amino acid numbering is based on DCAF1 Isoform 1 (Accession No. Q9Y4B6-1), cysteine residue C1112 of DCAF1, wherein the amino acid numbering is based on DCAF1 Isoform 2 (Accession No. Q9Y4B6-2), or cysteine residue C664 of DCAF1, wherein the amino acid numbering is based on DCAF1 Isoform 3 (Accession No. Q9Y4B6-3) and wherein the probe comprises an azetidinyl acrylamide moiety.
A compound of Formula (I)
Dependencies are inferred from the claim text.