Compounds and uses thereof

1. A compound having the structure of Formula I:

wherein

A is:

wherein

A 1 is a bond between A and L;

s and w are, independently 0, 1, 2, 3 or 4;

R 4 is H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 1 -C 6 heteroalkyl, or optionally substituted C 3 -C 10 carbocyclyl,

R 5 is H, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 3 -C 10 carbocyclyl, or optionally substituted C 6 -C 10 aryl;

R 6a is H, halogen, cyano, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 3 -C 10 carbocyclyl, optionally substituted C 2 -C 9 heterocyclyl, optionally substituted C 6 -C 10 aryl, optionally substituted C 2 -C 9 heteroaryl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 heteroalkenyl, hydroxy, thiol, or optionally substituted amino;

R 6b is H, halogen, cyano, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 3 -C 10 carbocyclyl, optionally substituted C 2 -C 9 heterocyclyl, optionally substituted C 6 -C 10 aryl, optionally substituted C 2 -C 9 heteroaryl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 heteroalkenyl, hydroxy, thiol, or optionally substituted amino, or R 6a and R 6b , together with the carbon atoms to which each is attached, combine to form optionally substituted C 6 -C 10 aryl or optionally substituted C 2 -C 9 heteroaryl;

R 7 is H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 1 -C 6 heteroalkyl, or optionally substituted C 3 -C 10 carbocyclyl;

R 8 is H, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 3 -C 10 carbocyclyl, or optionally substituted C 6 -C 10 aryl;

each R 9 is, independently, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 3 -C 10 carbocyclyl, optionally substituted C 2 -C 9 heterocyclyl, optionally substituted C 6 -C 10 aryl, optionally substituted C 2 -C 9 heteroaryl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 heteroalkenyl, hydroxy, thiol, or optionally substituted amino;

X 2 is N or CR 10b ;

R 10b is H, halogen, hydroxy, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 3 -C 10 carbocyclyl, optionally substituted C 2 -C 9 heterocyclyl, optionally substituted C 6 -C 10 aryl, optionally substituted C 2 -C 9 heteroaryl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 heteroalkenyl, hydroxy, thiol, or optionally substituted amino;

R 34 is H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 1 -C 6 heteroalkyl, or optionally substituted C 3 -C 10 carbocyclyl;

R 35 is H, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 3 -C 6 carbocyclyl, or optionally substituted C 6 -C 10 aryl;

each R 36 is, independently, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 3 -C 10 carbocyclyl, optionally substituted C 2 -C 9 heterocyclyl, optionally substituted C 6 -C 10 aryl, optionally substituted C 2 -C 9 heteroaryl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 heteroalkenyl, hydroxy, thiol, or optionally substituted amino;

R 37 is H, optionally substituted C 1 -C 6 alkyl, or optionally substituted C 1 -C 6 heteroalkyl; and

R 39 is H, halogen, optionally substituted C 1 -C 6 alkyl, or optionally substituted C 6 -C 10 aryl;

B is:

wherein

A 2 is a bond between B and L; and

R A5 is H, optionally substituted C 1 -C 6 alkyl, or optionally substituted C 1 -C 6 heteroalkyl;

L is:

wherein

A 1 is a bond between the linker and A;

A 2 is a bond between B and the linker;

n is 0 or 1;

p is 0 or 1;

each of E 1 and E 2 is, independently, O, S, NR N , optionally substituted C 1-10 alkylene, optionally substituted C 2-10 alkenylene, optionally substituted C 2-10 alkynylene, optionally substituted C 2 -C 10 polyethylene glycol, or optionally substituted C 1-10 heteroalkylene;

E 3 is optionally substituted C 1 -C 6 alkylene, optionally substituted C 1 -C 6 heteroalkylene, O, S, or NR N ;

each R N is, independently, H, optionally substituted C 1-4 alkyl, optionally substituted C 2-4 alkenyl, optionally substituted C 2-4 alkynyl, optionally substituted C 2-6 heterocyclyl, optionally substituted C 6-12 aryl, or optionally substituted C 1-7 heteroalkyl; and

each of F 1 , F 2 , and F 3 is, independently, optionally substituted C 3 -C 10 carbocyclylene, optionally substituted C 2-10 heterocyclylene, optionally substituted C 6 -C 10 arylene, or optionally substituted C 2 -C 9 heteroarylene,

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein E 1 is —CH 2 —.

3. The compound of claim 1 , wherein E 2 is O, NR w ,

wherein

c is 0, 1, 2, 3, 4, 5, 6, 7, or 8;

d is 0, 1, 2, or 3;

e is 0, 1, 2, 3, 4, 5, or 6;

f is 0, 1, 2, 3, or 4;

R d is H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, or optionally substituted C 3 -C 6 carbocyclyl;

R e is H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, or optionally substituted C 3 -C 6 carbocyclyl;

R f is H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, or optionally substituted C 3 -C 6 carbocyclyl;

R g is H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, or optionally substituted C 3 -C 6 carbocyclyl; and

W is O or NR w , wherein R w is H or optionally substituted C 1 -C 6 alkyl.

4. The compound of claim 3 , wherein E 2 is —NR N —.

5. The compound of claim 4 , wherein E 2 is —NH—.

6. The compound of claim 1 , wherein n is 1 and E 3 is

where a is 0 1, 2, 3, 4, or 5.

7. The compound of claim 1 , wherein F 1 is

8. The compound of claim 1 , wherein F 2 is

9. The compound of claim 1 , wherein F 3 is optionally substituted C 6 -C 10 arylene.

10. The compound of claim 1 , wherein:

E 1 is —CH 2 —;

E 2 is O, NR w ,

wherein

c is 0, 1, 2, 3, 4, 5, 6, 7, or 8;

d is 0, 1, 2, or 3;

e is 0, 1, 2, 3, 4, 5, or 6;

f is 0, 1, 2, 3, or 4;

R d is H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, or optionally substituted C 3 -C 6 carbocyclyl;

R e is H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, or optionally substituted C 3 -C 6 carbocyclyl;

R f is H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, or optionally substituted C 3 -C 6 carbocyclyl;

R g is H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, or optionally substituted C 3 -C 6 carbocyclyl;

W is O or NR w , wherein R w is H or optionally substituted C 1 -C 6 alkyl;

n is 0 or 1;

E 3 is

where a is 0, 1, 2, 3, 4, or 5; and

F 1 is

and

F 3 is optionally substituted C 6 -C 10 arylene.

11. The compound of claim 1 , wherein p is 1.

12. The compound of claim 10 , wherein p is 1.