HER3 ligands and uses thereof

1. A compound having the formula:

or a pharmaceutically acceptable salt thereof;

wherein

Y is 0 or 1;

W 1 is C(R 6 );

R 1 is independently a halogen, —CX 1 3 , —CHX 1 2 , —CH 2 X 1 , —CN, —SO n1 R 10 , —SO v1 NR 7 R 8 , —NHNH 2 , —ONR 7 R 8 , —NHC═(O)NHNH 2 , —NHC═(O)NR 7 R 8 , —N(O) m1 , —NR 7 R 8 , —C(O)R 9 , —C(O)—OR 9 , —C(O)NR 7 R 8 , —OR 10 , —NR 7 SO 2 R 10 , —NR 7 C═(O)R 9 , —NR 7 C(O)—OR 9 , —NR 7 OR 9 , —OCX 1 3 , —OCHX 1 2 , —OCH 2 X 1 , 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 adjacent R 1 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;

R 2 is independently a halogen, —CX 2 3 , —CHX 2 2 , —CH 2 X 2 , —CN, —SO n2 R 14 , —SO v2 NR 11 R 12 , —NHNH 2 , —ONR 11 R 12 , —NHC═(O)NHNR 11 R 12 , —NHC═(O)NR 11 R 12 , —N(O) m2 , —NR 11 R 12 , —C(O)R 13 , —C(O)—OR 9 , —C(O)NR 11 R 12 , —OR 14 , —NR 11 SO 2 R 14 , —NR 11 C═(O)R 13 , —NR 11 C(O)—OR 13 , —NR 11 OR 13 , —OCX 2 3 , —OCHX 2 2 , —OCH 2 X 2 , 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 adjacent R 2 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;

R 3 is independently a halogen, —CX 3 3 , —CHX 3 2 , —CH 2 X 3 , —CN, —SO n3 R 18 , —SO v3 NR 15 R 16 , —NHNH 2 , —ONR 15 R 16 , —NHC═(O)NHNR 15 R 16 , —NHC═(O)NR 15 R 16 , —N(O) m3 , —NR 15 R 16 , —C(O)R 17 , —C(O)—OR 17 , —C(O)NR 15 R 16 , —OR 18 , —NR 15 SO 2 R 17 , —NR 15 C═(O)R 17 , —NR 15 C(O)—OR 17 , —NR 15 OR 17 , —OCX 3 3 , —OCHX 3 2 , —OCH 2 X 3 , 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 adjacent R 3 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;

R 4 is a hydrogen, halogen, —CX 4 3 , —CHX 4 2 , —CH 2 X 4 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC═(O)NHNH 2 , —NHC═(O)NH 2 , —NHSO 2 H, —NHC═(O)H, —NHC(O)—OH, —NHOH, —OCX 4 3 , —OCHX 4 2 , —OCH 2 X 4 2 , 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;

R 5 is a hydrogen, halogen, —CX 5 3 , —CHX 5 2 , —CH 2 X 5 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC═(O)NHNH 2 , —NHC═(O) NH 2 , —NHSO 2 H, —NHC═(O)H, —NHC(O)—OH, —NHOH, —OCX 5 3 , —OCHX 5 2 , —OCH 2 X 5 , 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;

R 6 is halogen, —CX 6 3 , —CHX 6 2 , —CH 2 X 6 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC═(O)NHNH 2 , —NHC═(O) NH 2 , —NHSO 2 H, —NHC═(O)H, —NHC(O)—OH, —NHOH, —OCX 6 3 , —OCHX 6 2 , —OCH 2 X 6 , 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;

R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , and R 18 are independently hydrogen, halogen, —CX A 3 , —CHX A 2 , —CH 2 X A , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC═(O)NHNH 2 , —NHC═(O) NH 2 , —NHSO 2 H, —NHC═(O)H, —NHC(O)—OH, —NHOH, —OCX A 3 , —OCHX A 2 , —OCH 2 X A , 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; R 7 and R 8 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; R 11 and R 12 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; R 15 and R 16 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;

L 4 is a bond or a divalent linker;

L 5 is a bond or a divalent linker;

z1 and z2 are independently an integer from 0 to 4;

z3 is an integer from 0 to 5;

m1, m2, m3, v1, v2, and v3 are independently 1 or 2;

n1, n2, and n3 are independently an integer from 0 to 4; and

X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , and X A are independently —Cl, —Br, —I, or —F.

2. The compound of claim 1 , wherein

R 1 is independently a halogen, —CX 1 3 , —CHX 1 2 , —CH 2 X 1 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, substituted or unsubstituted C 1 -C 4 alkyl, or 2 to 4 membered substituted or unsubstituted heteroalkyl;

R 2 is independently a halogen, —CX 2 3 , —CHX 2 2 , —CH 2 X 2 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, substituted or unsubstituted C 1 -C 4 alkyl, or 2 to 4 membered substituted or unsubstituted heteroalkyl;

R 6 is halogen, —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, substituted or unsubstituted C 1 -C 4 alkyl, or 2 to 4 membered substituted or unsubstituted heteroalkyl;

L 4 is L 4A -L 4B -L 4C and L 4A , L 4B , and L 4C are each independently a bond, —O—, —NH—, —C(O)—, —C(O)NH—, —NHC(O)—, —C(O)O—, —OC(O)—, —NHC(O)NH—, —S—, 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; and

L 5 is L 5A -L 5B -L 5C and L 5A , L 5B , and L 5C are each independently a bond, —O—, —NH—, —C(O)—, —C(O)NH—, —NHC(O)—, —C(O)O—, —OC(O)—, —NHC(O)NH—, —S—, 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.

3. The compound of claim 1 , wherein z1 and z2 are 0.

4. The compound of claim 1 , wherein R 3 is independently —CF 3 or halogen.

5. The compound of claim 1 , wherein R 6 is —CN.

6. The compound of claim 1 , wherein -L 4 -R 4 is unsubstituted methoxy.

7. The compound of claim 1 , wherein R 4 is —NH 2 .

8. The compound of claim 1 , wherein -L 5 -R 5 is unsubstituted methoxy.

9. The compound of claim 1 , wherein R 5 is —NH 2 .

10. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

11. The pharmaceutical composition of claim 10 , further comprising an anti-cancer agent.

12. The compound of claim 1 , wherein z3 is 1.

13. The compound of claim 1 , having the formula