Modified proteins and protein degraders

A ligand comprising a DNA damage-binding protein 1 (DDB1) binding moiety, wherein the ligand is a heterobifunctional ligand comprising the structure of Formula (IIc), Formula (IId), or Formula (IIe):

• or a pharmaceutically acceptable salt thereof,
• wherein:
• F2 is a 5-membered heteroaryl;
• L2 is a bond, —C(═O)NR13—, —NR13C(═O)—, —C(═O)—, —C(═S)—, —S—, —S(═O), —S(═O)2—, —S(═O)NR13—, —NR13S(═O)—, —S(═O)2NR13—, —NR13S(═O)2—, —O—, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 heteroalkyl, C1-C4 alkoxy, C1-C4 alkylamino, C1-C4 alkenyl, or C1-C4 alkynyl, wherein each R13 is independently hydrogen, —S(═O)Rb, —S(═O)2Rd, —S(═O)2NRcRd, —C(═O)Rb, —CO2Ra, —C(═O)NRcRd, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C3-C8 carbocyclyl, C2-C8 heterocyclyl, aryl, or heteroaryl;
• wherein the alkyl, alkenyl, alkynyl, and heteroalkyl is optionally substituted with one, two, or three of halogen, —ORa, or —NRcRd;
• and the carbocyclyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one, two, or three of halogen, C1-C6 alkyl, C1-C6 haloalkyl, —ORa, or —NRcRd;
• each R11 and R12 is independently hydrogen, halogen, —CN, —Ra, —ORa, —SRa, —S(═O)Rb, —NO2, —NRcRd, —S(═O)2Rd, —NRaS(═O)2Rd, —S(═O)2NRcRd, —C(═O)Rb, —OC(═O)Rb, —CO2Ra, —OCO2Ra, —C(═O)NRcRd, —OC(═O)NRcRd, —NRaC(═O)NRcRd, —NRaC(═O)Rb, —NRaC(═O)ORaC1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C3-C8 carbocyclyl, C2-C8 heterocyclyl, aryl, or heteroaryl, wherein the alkyl, alkenyl, alkynyl, and heteroalkyl is optionally substituted with one, two, or three of halogen, —Ra, —ORa, or NRcRd;
• and the carbocyclyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one, two, or three of halogen, C1-C6 alkyl, C1-C6 haloalkyl, —Ra, —ORa, or —NRcRd;
• each Ra is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C3-C8 carbocyclyl, C2-C8 heterocyclyl, aryl, or heteroaryl, wherein the alkyl, alkenyl, alkynyl, and heteroalkyl is optionally substituted with one, two, or three of halogen, —OH, —OMe, or —NH2;
• and the carbocyclyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one, two, or three of halogen, C1-C6 alkyl, C1-C6 haloalkyl, —OH, —OMe, or —NH2;
• each Rb is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C3-C8 carbocyclyl, C2-C8 heterocyclyl, aryl, or heteroaryl, wherein the alkyl, alkenyl, alkynyl, and heteroalkyl is optionally substituted with one, two, or three of halogen, —OH, —OMe, or —NH2;
• and the carbocyclyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one, two, or three of halogen, C1-C6 alkyl, C1-C6 haloalkyl, —OH, —OMe, or —NH2;
• each Rc and Rd is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C3-C8 carbocyclyl, C2-C8 heterocyclyl, aryl, or heteroaryl, wherein the alkyl, alkenyl, alkynyl, and heteroalkyl is optionally substituted with one, two, or three of halogen, —OH, —OMe, or —NH2;
• and the carbocyclyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one, two, or three of halogen, C1-C6 alkyl, C1-C6 haloalkyl, —OH, —OMe, or —NH2;
• each Rc and Rd, together with the nitrogen atom to which they are attached, form a heterocyclyl or heteroaryl, wherein the heterocyclyl and heteroaryl is optionally substituted with one, two, or three of halogen, C1-C6 alkyl, C1-C6 haloalkyl, —OH, —OMe, or —NH2;
• q is an integer of 1-4;
• s is an integer of 1-5;
• L1 is a linker;
• and
• Z1 is a target protein binding moiety.