Methods and compounds for targeted autophagy

A compound comprising a monovalent cellular component binder covalently bound to a monovalent targeted autophagy protein binder, wherein the monovalent targeted autophagy protein binder is a monovalent form of the formula:

• wherein z1 is an integer from 0 to 7, z2 is an integer from 0 to 5, and z5 is 1 or 2;
• R1 is independently oxo, halogen, —CX13, —CHX12, —CH2X1, —OCX13, —OCH2X1, —OCHX12, —CN, —SOn1R1D, —SOv1NR1AR1B, —NHC(O)NR1AR1B, —N(O)m1, —NR1AR1B, —C(O)R1C, —C(O)—OR1C, —C(O)NR1AR1B, —OR1D, —NR15ASO2R1D, —NR1AC(O)R1C, —NR1AC(O)OR1C, —NR1AOR1C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• two R1 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R2 is independently oxo, halogen, —CX23, —CHX22, —CH2X2, —OCX23, —OCH2X2, —OCHX22, —CN, —SOn2R2D, —SOv2NR2AR2B, —NHC(O)NR2AR2B, —N(O)m2, —NR2AR2B, —C(O)R2C, —C(O)—OR2C, —C(O)NR2AR2B, OR2D, —NR2AR2D, —NR2AC(O)R2C, —NR2AC(O)OR2C, —N R2AOR2C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• two R2 sub stituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R4 is hydrogen, halogen, —CX43, —CHX42, —CH2X4, —OCX43, —OCH2X4, —OCHX42, —CN, —SOn4R4D, —SOv4NR4AR4B, —NHC(O)NR4AR4B, —N(O)m4, —NR4AR4B, —C(O)R4C, —C (O)—OR4C, —C(O)NR4AR4B, OR4D, —NR4ASO2R4D, —NR4AC(O)NR4C, —NR4AC(O)OR4C, —NR4AOR4C, E, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• E is an electrophilic moiety;
• L5 is a bond, —S(O)2—, —S(O)—,—NR5—, ═N—, —O—, —S—, —C(O)—, —C(O)NR5—, —NR5C(O)—, —NR5C(O)NH—, —NHC(O)NR5—, —C(O)O—, —OC(O)—, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene;
• R5 is hydrogen, —CX53, —CHX52, —CH2X5, —OCX53, —OCH2X5, —OCHX52, —CN, —C(O)R5C, —C(O)—OR5C, —C(O)NR5AR5B, —OR5D, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• L6 is a bond, —S(O)2—, —S(O)—, —NR6—, ═N—, —O—, —S—, —C(O)—, —C(O)NR6—, —NR6C(O)—, —NR6C(O)NH—, —NHC(O)NR6—, —C(O)O—, —OC(O)—, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene;
• R6 is hydrogen, —CX63, —CHX62, —CH2X6, —OCX63, —OCH2X6, —OCHX62, —CN, —C(O)R6C, —C(O)—OR6C, —C(O)NR6AR6B, —OR6D, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R1A, R1B, R1C, R1D, R2A, R2B, R2C, R2D, R3A, R3B, R3C, R3D, R4A, R4B, R4C, R4D, R5A, R5B, R5C, R5D, R6A, R6B, R6C, and R6D are independently hydrogen, —CX3, —CN, —COOH, —CONH2, —CHX2, —CH2X, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R1A and R1B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R2A and R2B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R4A and R4B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R5A and R5B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R6A and R6B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• X, X1, X2, X4, X5, and X6 are independently —F, —Cl, —Br, or —I;
• n1, n2, n4, n5, and n6 are independently an integer from 0 to 4;
• and
• m1, m2, m4, m5, m6, v1, v2, v4, v5, and v6 are independently 1 or 2.

A method of reducing the level of a cellular component, said method comprising contacting a cellular component with a targeted autophagy degrader;

• wherein the targeted autophagy degrader comprises:
• i) a monovalent autophagy associated protein binder;
• ii) a monovalent cellular component binder;
• and
• iii) a covalent linker directly bonded to the monovalent autophagy associated protein binder and the monovalent cellular component binder.