Substituted indoles and methods of use thereof

1. A compound of Formula IV:

wherein:

R 1d is fluoro;

Z 4 is selected from the group consisting of —O—, —C(R 28a )(R 28b )—, and —N(R 23 )—; or Z 4 is absent;

Z 5 is selected from the group consisting of —CH 2 — and —CH 2 CH 2 —;

R 11a is selected from the group consisting of optionally substituted alkyl, optionally substituted heterocyclo, optionally substituted heteroaryl, and —N(R 12b )C(═O)R 13c ;

R 12b is selected from the group consisting of hydrogen, alkyl, cycloalkyl, and heterocyclo, (C 1 -C 4 alkoxy)C 1 -C 4 alkyl, and (hydroxy)C 1 -C 4 alkyl;

R 13c is selected from the group consisting of alkyl, haloalkyl, alkoxy, (alkoxy)alkyl, (hydroxy)alkyl, (cyano)alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycle, amino, (amino)alkyl, (C 3 -C 6 cycloalkyl)oxy, and (4- to 8-membered heterocyclo)oxy;

R 23 is selected from the group consisting of hydrogen and C 1 -C 4 alkyl; and

R 28a and R 28b are independently selected from the group consisting of hydrogen, alkyl, and halo;

or a pharmaceutically acceptable salt or solvate thereof.

2. The compound of claim 1 of Formula IV-A:

or a pharmaceutically acceptable salt or solvate thereof.

3. The compound of claim 2 , wherein:

R 11a is selected from the group consisting of:

(A) unsubstituted 4- to 14-membered heterocyclo;

(B) substituted 4- to 14-membered heterocyclo having one, two or three substituents independently selected from the group consisting of:

(i) —N(R 12a )C(═O)R 13a ; (ii) —C(═O)R 13b ; (iii) C 1 -C 4 alkyl; (iv) (C 1 -C 4 alkoxy)C 1 -C 4 alkyl; (v) (hydroxy)C 1 -C 4 alkyl; (vi) C 1 -C 4 haloalkyl; (vii) amino; (vii) hydroxy; (viii) —N(R 12a )S(═O) 2 R 24 ; (ix) —S(═O) 2 R 24 ; (x) unsubstituted C 3 -C 6 cycloalkyl; (xi) substituted C 3 -C 6 cycloalkyl having one or two substituents independently selected from the group consisting of halo, hydroxy, C 1 -C 4 alkyl, amino, and (amino)C 1 -C 4 alkyl; (xii) unsubstituted 4- to 14-membered heterocyclo; and substituted 4- to 14-membered heterocyclo having one or two substituents independently selected from the group consisting of amino, hydroxy, and C 1 -C 4 alkyl; (xiii) —C(═N—R 60 )R 61 ; and (xiv) —C(═C—NO 2 )R 64 ;

(C) unsubstituted 5- to 10-membered heteroaryl;

(D) substituted 5- or 6-membered heteroaryl having one, two, three, or four substituents independently selected from the group consisting of halo and C 1 -C 4 alkyl;

(E) C 1 -C 6 alkyl; and

(F) —N(R 12b )C(═O)R 13c ;

R 12a and R 12b are each independently selected from the group consisting of hydrogen, C 1 -C 4 alkyl, (C 1 -C 4 alkoxy)C 1 -C 4 alkyl, and (hydroxy)C 1 -C 4 alkyl;

R 13a , R 13b , and R 13c are each independently selected from the group consisting of (A) C 1 -C 6 alkyl; (B) C 1 -C 6 haloalkyl; (C) unsubstituted C 3 -C 6 cycloalkyl; (D) C 1 -C 6 alkoxy; (E) (C 1 -C 4 alkoxy)C 1 -C 4 alkyl; (F) (hydroxy)C 1 -C 4 alkyl; (G) (cyano)alkyl; (H) unsubstituted C 6 -C 10 aryl; (I) substituted C 6 -C 10 aryl, having one, two, three, or four substituents independently selected from the group consisting of halo, amino, hydroxy, and C 1 -C 4 alkyl; (J) unsubstituted 5- or 6-membered heteroaryl; (K) substituted 5- or 6-membered heteroaryl having one, two, three, or four substituents independently selected from the group consisting of halo, amino, hydroxy, and C 1 -C 4 alkyl; (L) unsubstituted 4- to 14-membered heterocyclo; (M) substituted 4- to 14-membered heterocyclo having one or two substituents independently selected from the group consisting of amino, hydroxy, and C 1 -C 4 alkyl; (N) amino; (0) (amino)alkyl; (P) (C 3 -C 6 cycloalkyl)oxy; and (Q) (4- to 8-membered heterocyclo)oxy;

R 24 is selected from the group consisting of C 1 -C 4 alkyl and (hydroxy)C 1 -C 4 alkyl;

R 60 is selected from the group consisting of cyano, nitro, hydroxy, C 1 -C 6 alkoxy, —C(═O)R 62 and —S(═O) 2 R 62 ;

R 61 is selected from the group consisting of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, and —NR 63a R 63b ;

R 62 is selected from the group consisting of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, and —NR 63a R 63b ;

R 63a is selected from the group consisting of hydrogen, C 1 -C 6 alkyl, and C 3 -C 6 cycloalkyl;

R 63b is selected from the group consisting of hydrogen, C 1 -C 6 alkyl, and C 3 -C 6 cycloalkyl; or

R 63a and R 63b taken together with the nitrogen atom to which they are attached form a 4- to 6-membered optionally substituted heterocyclo;

R 64 is selected from the group consisting of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, and —NR 63c R 63d ;

R 63c is selected from the group consisting of hydrogen, C 1 -C 6 alkyl, and C 3 -C 6 cycloalkyl; and

R 63d is selected from the group consisting of hydrogen, C 1 -C 6 alkyl, and C 3 -C 6 cycloalkyl; or

R 63c and R 63d taken together with the nitrogen atom to which they are attached form a 4- to 6-membered optionally substituted heterocyclo, or a pharmaceutically acceptable salt or solvate thereof.

4. The compound of claim 3 , wherein R 11a is a substituted 4- to 14-membered heterocyclo selected from the group consisting of:

R 12a is selected from the group consisting of hydrogen, C 1 -C 3 alkyl, (C 1 -C 4 alkoxy)C 1 -C 4 alkyl, and (hydroxy)C 1 -C 4 alkyl;

R 13a is selected from the group consisting of C 1 -C 4 alkyl; amino; unsubstituted C 3 -C 6 cycloalkyl; substituted C 3 -C 6 cycloalkyl having one or two substituents independently selected from the group consisting of halo, hydroxy, C 1 -C 4 alkyl, amino, and (amino)C 1 -C 4 alkyl; (C 1 -C 4 alkoxy)C 1 -C 4 alkyl; (hydroxy)C 1 -C 4 alkyl; unsubstituted 4- to 14-membered heterocyclo; and substituted 4- to 14-membered heterocyclo having one or two substituents independently selected from the group consisting of amino, hydroxy, and C 1 -C 4 alkyl;

R 13b is selected from the group consisting of C 1 -C 4 alkyl; amino; C 1 -C 4 haloalkyl; C 1 -C 4 alkoxy; (hydroxy)C 1 -C 4 alkyl; (C 1 -C 4 alkoxy)C 1 -C 4 alkyl; (amino)alkyl; unsubstituted C 3 -C 6 cycloalkyl; substituted C 3 -C 6 cycloalkyl having one or two substituents independently selected from the group consisting of halo, hydroxy, C 1 -C 4 alkyl, amino, and (amino)C 1 -C 4 alkyl; unsubstituted 4-to 14-membered heterocyclo; and substituted 4- to 14-membered heterocyclo having one or two substituents independently selected from the group consisting of amino, hydroxy, and C 1 -C 4 alkyl; (C 3 -C 6 cycloalkyl)oxy; and (4- to 8-membered heterocyclo)oxy;

R 21 is selected from the group consisting of hydrogen, —C(═O)R 13b , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, unsubstituted 4- to 14-membered heterocyclo, and —S(═O) 2 R 24 ;

R 22 is selected from the group consisting of C 1 -C 4 alkyl; unsubstituted C 3 -C 6 cycloalkyl; substituted C 3 -C 6 cycloalkyl having one or two substituents independently selected from the group consisting of halo, hydroxy, C 1 -C 4 alkyl, amino, and (amino)C 1 -C 4 alkyl; unsubstituted 4- to 14-membered heterocyclo; and substituted 4- to 14-membered heterocyclo having one or two substituents independently selected from the group consisting of amino, hydroxy, and C 1 -C 4 alkyl;

R 24 is selected from the group consisting of C 1 -C 4 alkyl and (hydroxy)C 1 -C 4 alkyl;

R 25 is selected from the group consisting of hydrogen, C 1 -C 4 alkyl, and C 1 -C 4 haloalkyl;

R 25b and R 25c are independently selected from the group consisting of C 1 -C 4 alkyl and C 1 -C 4 haloalkyl;

R 26 is selected from the group consisting of unsubstituted 4- to 14-membered heterocyclo; and substituted 4- to 14-membered heterocyclo having one or two substituents independently selected from the group consisting of amino, hydroxy, and C 1 -C 4 alkyl; and

R 21a and R 25a taken together with the atoms to which they are attached form an optionally substituted 4- to 8-membered heterocyclo, or a pharmaceutically acceptable salt or solvate thereof.

5. The compound of claim 3 , wherein R 11a is a substituted 4- to 14-membered heterocyclo selected from the group consisting of:

R 27a and R 27b are each independently selected from the group consisting of hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, (C 1 -C 4 alkoxy)C 1 -C 4 alkyl, and (hydroxy)C 1 -C 4 alkyl;

R 27c is selected from the group consisting of hydrogen; —C(═O)R 13b ; C 1 -C 4 alkyl; C 1 -C 4 haloalkyl; unsubstituted 4- to 14-membered heterocyclo; and substituted 4- to 14-membered heterocyclo having one or two substituents independently selected from the group consisting of amino, hydroxy, and C 1 -C 4 alkyl; and —S(═O) 2 R 24 ;

R 27d is selected from the group consisting of hydrogen; C 1 -C 4 alkyl; and C 1 -C 4 haloalkyl;

R 13b is selected from the group consisting of C 1 -C 4 alkyl; aminoC 1 -C 4 haloalkyl; C 1 -C 4 alkoxy; (hydroxy)C 1 -C 4 alkyl; (C 1 -C 4 alkoxy)C 1 -C 4 alkyl; (amino)alkyl; unsubstituted C 3 -C 6 cycloalkyl; substituted C 3 -C 6 cycloalkyl having one or two substituents independently selected from the group consisting of halo, hydroxy, C 1 -C 4 alkyl, amino, and (amino)C 1 -C 4 alkyl; unsubstituted 4-to 14-membered heterocyclo; substituted 4- to 14-membered heterocyclo having one or two substituents independently selected from the group consisting of amino, hydroxy, and C 1 -C 4 alkyl; (C 3 -C 6 cycloalkyl)oxy; and (4- to 8-membered heterocyclo)oxy; and

R 24 is selected from the group consisting of C 1 -C 4 alkyl and (hydroxy)C 1 -C 4 alkyl, or a pharmaceutically acceptable salt or solvate thereof.

6. The compound of claim 5 , wherein R 11a is a substituted 4- to 14-membered heterocyclo selected from the group consisting of:

or a pharmaceutically acceptable salt or solvate thereof.

7. The compound of claim 3 , wherein R 11a is a substituted 4- to 14-membered heterocyclo selected from the group consisting of:

or a pharmaceutically acceptable salt or solvate thereof.

8. The compound of claim 2 , wherein Z 4 is —CH 2 —, or a pharmaceutically acceptable salt or solvate thereof.

9. The compound of claim 2 , wherein R 11a is a substituted 4- to 14-membered heterocyclo is selected from the group consisting of

or a pharmaceutically acceptable salt or solvate thereof.

10. The compound of claim 9 , wherein: R 12a is selected from the group consisting of hydrogen and C 1 -C 3 alkyl; R 13a is C 1 -C 4 alkyl; and R 13b is C 1 -C 4 alkyl, or a pharmaceutically acceptable salt or solvate thereof.

11. The compound of claim 10 , wherein: R 12a is selected from the group consisting of hydrogen and methyl; R 13a is methyl; and R 13b is methyl, or a pharmaceutically acceptable salt or solvate thereof.

12. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt or solvate thereof.

13. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier.

14. A method of treating a subject in need thereof, the method comprising administering to the subject the compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein the subject has multiple myeloma.

15. A kit comprising the compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, and instructions for administering the compound, or a pharmaceutically acceptable salt or solvate thereof, to a subject having multiple myeloma, diffuse large B-cell lymphoma, or renal cell carcinoma.

16. A method, comprising administering a compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, to a subject in need thereof, wherein: (a) the subject has multiple myeloma; and (b) the multiple myeloma is characterized as having a chromosomal translocation.

17. The compound of claim 12 that is:

or a pharmaceutically acceptable salt or solvate thereof.

18. The compound of claim 12 that is:

or a pharmaceutically acceptable salt thereof.

19. The compound of claim 12 that is:

or a pharmaceutically acceptable solvate thereof.

20. The compound of claim 12 that is:

21. The compound of claim 12 that is:

or a pharmaceutically acceptable salt or solvate thereof.

22. The compound of claim 12 that is:

or a pharmaceutically acceptable salt or solvate thereof.

23. The compound of claim 2 , wherein:

Z 4 is —CH 2 —;

R 11a is selected from the group consisting of:

R 12a is selected from the group consisting of hydrogen and C 1 -C 3 alkyl;

R 21 is —C(═O)R 13b ;

R 27c is —C(═O)R 13b ;

R 13b is selected from the group consisting of C 1 -C 4 alkyl and (hydroxy)C 1 -C 4 alkyl;

R 24 is C 1 -C 4 alkyl;

R 25 is selected from the group consisting of hydrogen, C 1 -C 4 alkyl, and C 1 -C 4 haloalkyl; and

R 25b and R 25c are independently selected from the group consisting of C 1 -C 4 alkyl and C 1 -C 4 haloalkyl, or a pharmaceutically acceptable salt or solvate thereof.

24. A compound of Formula IV:

wherein:

R 1d is selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, (hydroxy)alkyl, and alkoxy;

Z 4 is selected from the group consisting of —O— and —CH 2 —; or Z 4 is absent;

Z 5 is selected from the group consisting of —CH 2 — and —CH 2 CH 2 —;

R 11a is selected from the group consisting of optionally substituted alkyl, optionally substituted heterocyclo, optionally substituted heteroaryl, and —N(R 12b )C(═O)R 13c ;

R 12b is selected from the group consisting of hydrogen and alkyl; and

R 13c is selected from the group consisting of alkyl, haloalkyl, alkoxy, (alkoxy)alkyl, (hydroxy)alkyl, (cyano)alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, and optionally substituted heterocycle,

or a pharmaceutically acceptable salt or solvate thereof.

25. The compound of claim 24 of Formula IV-A:

or a pharmaceutically acceptable salt or solvate thereof.

26. The compound of claim 25 , wherein:

R 11a is selected from the group consisting of:

(A) unsubstituted 4- to 14-membered heterocyclo;

(B) substituted 4- to 14-membered heterocyclo having one, two or three substituents independently selected from the group consisting of:

(i) —N(R 12a )C(═O)R 13a ; (ii) —C(═O)R 13b ; and (iii) C 1 -C 4 alkyl;

(C) unsubstituted 5- to 10-membered heteroaryl;

(D) substituted 5- or 6-membered heteroaryl having one, two, three, or four substituents independently selected from the group consisting of halo and C 1 -C 4 alkyl;

(E) C 1 -C 6 alkyl; and

(F) —N(R 12b )C(═O)R 13c ;

R 12a and R 12b are each independently selected from the group consisting of hydrogen and C 1 -C 4 alkyl;

R 13a , R 13b , and R 13c are each independently selected from the group consisting of (A) C 1 -C 6 alkyl; (B) C 1 -C 6 haloalkyl; (C) unsubstituted C 3 -C 6 cycloalkyl; (D) C 1 -C 6 alkoxy; (E) (C 1 -C 4 alkoxy)C 1 -C 4 alkyl; (F) (hydroxy)C 1 -C 4 alkyl; (G) (cyano)alkyl; (H) unsubstituted C 6 -C 10 aryl; (I) substituted C 6 -C 10 aryl, having one, two, three, or four substituents independently selected from the group consisting of halo, amino, hydroxy, and C 1 -C 4 alkyl; (J) unsubstituted 5- or 6-membered heteroaryl; (K) substituted 5- or 6-membered heteroaryl having one, two, three, or four substituents independently selected from the group consisting of halo, amino, hydroxy, and C 1 -C 4 alkyl; (L) unsubstituted 4- to 14-membered heterocyclo; and (M) substituted 4- to 14-membered heterocyclo having one or two substituents independently selected from the group consisting of amino, hydroxy, and C 1 -C 4 alkyl, or a pharmaceutically acceptable salt or solvate thereof.

27. The compound of claim 25 , wherein Z 4 is —CH 2 —, or a pharmaceutically acceptable salt or solvate thereof.

28. The compound of claim 25 , wherein R 11a is a substituted 4- to 14-membered heterocyclo is selected from the group consisting of

or a pharmaceutically acceptable salt or solvate thereof.

29. The compound of claim 28 , wherein: R 12a is selected from the group consisting of hydrogen and C 1 -C 3 alkyl; R 13a is C 1 -C 4 alkyl; and R 13b is C 1 -C 4 alkyl, or a pharmaceutically acceptable salt or solvate thereof.

30. The compound of claim 29 , wherein: R 12a is selected from the group consisting of hydrogen and methyl; R 13a is methyl; and R 13b is methyl, or a pharmaceutically acceptable salt or solvate thereof.

31. The compound of claim 25 , wherein R 1d is fluoro, or a pharmaceutically acceptable salt or solvate thereof.

32. A method of treating a subject in need thereof, the method comprising administering to the subject the compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein the subject has diffuse large B-cell lymphoma.

33. A method of treating a subject in need thereof, the method comprising administering to the subject the compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein the subject has renal cell carcinoma.

34. The method of claim 16 , wherein the chromosomal translocation is a t(4;14) translocation.

35. A method, comprising administering the compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, to a subject in need thereof, wherein:

(a) the subject has multiple myeloma; and

(b) the multiple myeloma is characterized as having an overexpression of WHSC1/NSD2/MMSET.

36. A pharmaceutical composition comprising the compound of claim 24 , or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier.

37. A method of treating a subject in need thereof, the method comprising administering to the subject the compound of claim 24 , or a pharmaceutically acceptable salt or solvate thereof, wherein the subject has multiple myeloma.

38. A method of treating a subject in need thereof, the method comprising administering to the subject the compound of claim 24 , or a pharmaceutically acceptable salt or solvate thereof, wherein the subject has diffuse large B-cell lymphoma.

39. A method of treating a subject in need thereof, the method comprising administering to the subject the compound of claim 24 , or a pharmaceutically acceptable salt or solvate thereof, wherein the subject has renal cell carcinoma.

40. A method, comprising administering the compound of claim 24 , or a pharmaceutically acceptable salt or solvate thereof, to a subject in need thereof, wherein: (a) the subject has multiple myeloma; and (b) the multiple myeloma is characterized as having a chromosomal translocation.

41. The method of claim 40 , wherein the chromosomal translocation is a t(4;14) translocation.

42. A method, comprising administering the compound of claim 24 , or a pharmaceutically acceptable salt or solvate thereof, to a subject in need thereof, wherein:

(a) the subject has multiple myeloma; and

(b) the multiple myeloma is characterized as having an overexpression of WHSC1/NSD2/MMSET.

43. A pharmaceutical composition comprising the compound of claim 17 , or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier.

44. A method of treating a subject in need thereof, the method comprising administering to the subject the compound of claim 17 , or a pharmaceutically acceptable salt or solvate thereof, wherein the subject has multiple myeloma.

45. A method of treating a subject in need thereof, the method comprising administering to the subject the compound of claim 17 , or a pharmaceutically acceptable salt or solvate thereof, wherein the subject has diffuse large B-cell lymphoma.

46. A method of treating a subject in need thereof, the method comprising administering to the subject the compound of claim 17 , or a pharmaceutically acceptable salt or solvate thereof, wherein the subject has renal cell carcinoma.

47. A method, comprising administering the compound of claim 17 , or a pharmaceutically acceptable salt or solvate thereof, to a subject in need thereof, wherein: (a) the subject has multiple myeloma; and (b) the multiple myeloma is characterized as having a chromosomal translocation.

48. The method of claim 47 , wherein the chromosomal translocation is a t(4;14) translocation.

49. A method, comprising administering the compound of claim 17 , or a pharmaceutically acceptable salt or solvate thereof, to a subject in need thereof, wherein:

(a) the subject has multiple myeloma; and

(b) the multiple myeloma is characterized as having an overexpression of WHSC1/NSD2/MMSET.

50. A pharmaceutical composition comprising the compound of claim 18 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

51. A method of treating a subject in need thereof, the method comprising administering to the subject the compound of claim 18 , or a pharmaceutically acceptable salt thereof, wherein the subject has multiple myeloma.

52. A method of treating a subject in need thereof, the method comprising administering to the subject the compound of claim 18 , or a pharmaceutically acceptable salt thereof, wherein the subject has diffuse large B-cell lymphoma.

53. A method of treating a subject in need thereof, the method comprising administering to the subject the compound of claim 18 , or a pharmaceutically acceptable salt thereof, wherein the subject has renal cell carcinoma.

54. A method, comprising administering the compound of claim 18 , or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein: (a) the subject has multiple myeloma; and (b) the multiple myeloma is characterized as having a chromosomal translocation.

55. The method of claim 54 , wherein the chromosomal translocation is a t(4;14) translocation.

56. A method, comprising administering the compound of claim 18 , or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein:

(a) the subject has multiple myeloma; and

(b) the multiple myeloma is characterized as having an overexpression of WHSC1/NSD2/MMSET.

57. A pharmaceutical composition comprising the compound of claim 19 , or a pharmaceutically acceptable solvate thereof, and a pharmaceutically acceptable carrier.

58. A method of treating a subject in need thereof, the method comprising administering to the subject the compound of claim 19 , or a pharmaceutically acceptable solvate thereof, wherein the subject has multiple myeloma.

59. A method of treating a subject in need thereof, the method comprising administering to the subject the compound of claim 19 , or a pharmaceutically acceptable solvate thereof, wherein the subject has diffuse large B-cell lymphoma.

60. A method of treating a subject in need thereof, the method comprising administering to the subject the compound of claim 19 , or a pharmaceutically acceptable solvate thereof, wherein the subject has renal cell carcinoma.

61. A method, comprising administering the compound of claim 19 , or a pharmaceutically acceptable solvate thereof, to a subject in need thereof, wherein: (a) the subject has multiple myeloma; and (b) the multiple myeloma is characterized as having a chromosomal translocation.

62. The method of claim 61 , wherein the chromosomal translocation is a t(4;14) translocation.

63. A method, comprising administering the compound of claim 19 , or a pharmaceutically acceptable solvate thereof, to a subject in need thereof, wherein:

(a) the subject has multiple myeloma; and

(b) the multiple myeloma is characterized as having an overexpression of WHSC1/NSD2/MMSET.

64. A pharmaceutical composition comprising the compound of claim 20 and a pharmaceutically acceptable carrier.

65. A method of treating a subject in need thereof, the method comprising administering to the subject the compound of claim 20 wherein the subject has multiple myeloma.

66. A method of treating a subject in need thereof, the method comprising administering to the subject the compound of claim 20 wherein the subject has diffuse large B-cell lymphoma.

67. A method of treating a subject in need thereof, the method comprising administering to the subject the compound of claim 20 , wherein the subject has renal cell carcinoma.

68. A method, comprising administering the compound of claim 20 to a subject in need thereof, wherein: (a) the subject has multiple myeloma; and (b) the multiple myeloma is characterized as having a chromosomal translocation.

69. The method of claim 68 , wherein the chromosomal translocation is a t(4;14) translocation.

70. A method, comprising administering the compound of claim 20 to a subject in need thereof, wherein:

(a) the subject has multiple myeloma; and

(b) the multiple myeloma is characterized as having an overexpression of WHSC1/NSD2/MMSET.