Double degraders and uses thereof

A compound of formula I-IV:

• or a pharmaceutically acceptable salt thereof, wherein:
• LBM is an E3 ubiquitin ligase binding moiety of formula:
• or a pharmaceutically acceptable salt thereof, wherein:
• X1 is —C(O)—;
• X2 is a carbon atom;
• X3 is —CR2—;
• R1 is hydrogen;
• each R2 is independently hydrogen, C1-6 aliphatic, halogen, or —OR;
• Ring A is
• Ring B is a fused 6-membered aryl;
• R3 is hydrogen;
• R4 is C1-6 aliphatic;
• L1 is a covalent bond;
• m is 0, 1, or 2;
• and
• each R is independently hydrogen or C1-6 aliphatic,
• or a pharmaceutically acceptable salt thereof, wherein:
• each of X1, X2, and X3 is independently selected from —CH2— and —C(O)—;
• R1 is hydrogen;
• each of R2 is independently hydrogen, C1-6 aliphatic, halogen, or —OR;
• Ring A is a fused 6-membered aryl;
• m is 0, 1, or 2, 3 or 4;
• and
• each R is independently hydrogen or C1-6 aliphatic, or
• or a pharmaceutically acceptable salt thereof, wherein:
• X4, X5, and X6 are each independently selected from —CR2— and —C(O)—;
• each R is independently hydrogen or C1-6 aliphatic;
• R6 is C1-6 aliphatic;
• Ring D is phenyl;
• each R7 is independently hydrogen, C1-6 aliphatic, halogen, —OR, or
• and
• p is 0, 1, or 2;
• IBM is an IRAK binding moiety of formula I-aaa:
• or a pharmaceutically acceptable salt thereof, wherein:
• Ring W is cyclohexyl or
• Ring X is phenyl,
• Ring Y is phenyl or a 5-10 membered monocyclic or bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• Lv and Lw are covalent bonds;
• each Rw is independently hydrogen, C1-6 aliphatic, halogen, or —OR;
• each R is independently hydrogen or C1-6 aliphatic;
• each Rx is independently hydrogen, C1-6 aliphatic, halogen, or —OR;
• Rz is selected from
• or hydrogen;
• Ring Z a 4-10 membered saturated monocyclic or bicyclic carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• each Ry is independently hydrogen, C1-6 aliphatic, halogen, or —OR;
• w is 0, 1, or 2;
• x is 0, 1, or 2;
• and
• y is 0, 1, or 2;
• BBM is a BTK binding moiety of formula:
• or a pharmaceutically acceptable salt thereof, wherein:
• Q is CH or N;
• G is a covalent bond;
• Ring U is phenyl;
• each Ru is independently hydrogen, C1-6 aliphatic, halogen, or —OR;
• Ring V is a 4-10 membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic, or spirocyclic carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• each Rv is independently hydrogen, C1-6 aliphatic, halogen, or —OR;
• each R is independently hydrogen or C1-6 aliphatic;
• u is 0, 1, or 2;
• and
• v is 0, 1, or 2;
• or
• or a pharmaceutically acceptable salt thereof, wherein:
• Ring S is phenyl;
• each Rs is independently hydrogen, C1-6 aliphatic, halogen, or —OR;
• each R is independently hydrogen or C1-6 aliphatic;
• Ring T is phenyl or a 5-10 membered monocyclic or bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• each Rt is independently hydrogen, C1-6 aliphatic, halogen, or —OR;
• Ring U is phenyl;
• each Ru is independently hydrogen, C1-6 aliphatic, halogen, or —OR;
• Ring V is phenyl;
• each Rv is independently hydrogen, C1-6 aliphatic, halogen, or —OR;
• s is 0, 1, or 2;
• t is 0, 1, or 2;
• u is 0, 1, or 2;
• and
• v is 0, 1, or 2;
• each of La, Lb, Lc, Lx, Lz, and Ly is independently a covalent bond, —CO—, a C1-10 hydrocarbon chain, —NR—(CH2)1-10—, —(CH2)1-10—NR—(CH2)1-10—, —CONR—(CH2)1-10—, —(CH2)1-10-Cy-(CH2)1-10—NR—, -Cy-(CH2)1-10—, —(CH2)1-10-Cy-(CH2)1-10—,
• wherein each R is hydrogen or C1-6 aliphatic;
• each -Cy- is independently a bivalent ring selected from a 4-7 membered saturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 4-11 membered saturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and an 8-10 membered bicyclic saturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• and
• X is
• wherein R is hydrogen or C1-6 aliphatic.