Substituted heteroaryl fused derivatives as P13K inhibitors

1. A method of treating a disease selected from breast cancer, prostate cancer, colon cancer, brain cancer, bladder cancer, skin cancer, cancer of the uterus, ovary cancer, lung cancer, pancreatic cancer, renal cancer, gastric cancer, acute myeloblastic leukemia, chronic myeloid leukemia, and B cell lymphoma, in a patient, comprising administering to said patient a therapeutically effective amount of a compound of Formula I:

or a pharmaceutically acceptable salt thereof; wherein:

the symbol indicates that the ring is aromatic;

Z is O, S, or NR A ;

U is N; and V is C; or

U is C; and V is N;

X is N or CR 4 ; and Y is CR 5 or N; or

X is absent; and Y is S or O;

Ar is a purine ring, substituted with n independently selected R B groups; wherein n is 0, 1, or 2;

Cy is cycloalkyl, heterocycloalkyl, aryl or heteroaryl, each substituted with m independently selected R C groups; wherein m is 0, 1, 2, 3, 4, or 5;

R A is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl;

each R B is independently selected from —(C 1-4 alkyl) r -Cy 1 , halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halosulfanyl, CN, NO 2 , OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , C(═NR e )NR c1 R d1 , NR c1 C(═NR e )NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)OR a1 , NR c1 C(O)NR c1 R d1 , NR c1 S(O)R b1 , NR c1 S(O) 2 R b1 , NR c1 S(O) 2 NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 ;

each R C is independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halosulfanyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halosulfanyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c R d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d ;

R 1 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, and C 2-6 alkynyl; wherein said C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from halo, OH, CN, NR 1† R 2† , C 1-6 alkoxy, C 1-6 haloalkoxy, thio, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, carboxy, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, and C 1-6 alkylcarbonylamino;

each R 1† and R 2† is independently selected from H and C 1-6 alkyl;

or any R 1† and R 2† together with the N atom to which they are attached form a 3-, 4-, 5-, 6-, or 7-membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl;

R 2 , R 3 , R 4 , and R 5 are each independently selected from H, OH, CN, NO 2 , halo, C 1-6 alkyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, amino, C 1-4 alkylamino, di(C 1-6 alkyl)amino, thio, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, C 1-6 alkylcarbonyl, carboxy, C 1-6 alkoxycarbonyl, and C 1-6 alkylcarbonylamino;

each Cy 1 is, independently, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl, each optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halosulfanyl, CN, NO 2 , OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , C(═NR e )NR c1 R d1 , NR c1 C(═NR e )NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)OR a1 , NR c1 C(O)NR c1 R d1 , NR c1 S(O)R b1 , NR c1 S(O) 2 R b1 , NR c1 S(O) 2 NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 ;

each R a , R b , R c , and R d is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)NR c5 R d5 , NR c5 C(O)OR a5 , C(═NR f )NR c5 R d5 , NR c5 C(═NR f )NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , and S(O) 2 NR c5 R d5 ;

or any R c and R d together with the N atom to which they are attached form a 3-, 4-, 5-, 6-, or 7-membered heterocycloalkyl group or a heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)NR c5 R d5 , NR c5 C(O)OR a5 , C(═NR f )NR c5 R d5 , NR c5 C(═NR f )NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , and S(O) 2 NR c5 R d5 ;

each R e and R f is independently selected from H, C 1-6 alkyl, CN, OR a5 , SR b5 , S(O) 2 R b5 , C(O)R b5 , S(O) 2 NR c5 R d5 , and C(O)NR c5 R d5 ;

each R a1 , R b1 , R c1 , and R d1 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)NR c5 R d5 , NR c5 C(O)OR a5 , C(═NR f )NR c5 R d5 , NR c5 C(═NR f )NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , and S(O) 2 NR c5 R d5 ;

or any R c1 and R d1 together with the N atom to which they are attached form a 3-, 4-, 5-, 6-, or 7-membered heterocycloalkyl group or a heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)NR c5 R d5 , NR c5 C(O)OR a5 , C(═NR f )NR c5 R d5 , NR c5 C(═NR f )NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , and S(O) 2 NR c5 R d5 ;

each R a5 , R b5 , R c5 , and R d5 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, di(C 1-6 alkyl)amino, C 1-6 haloalkyl, and C 1-6 haloalkoxy;

or any R c5 and R d5 together with the N atom to which they are attached form a 3-, 4-, 5-, 6-, or 7-membered heterocycloalkyl group or heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, di(C 1-6 alkyl)amino, C 1-6 haloalkyl, and C 1-6 haloalkoxy; and

r is 0 or 1;

wherein treating refers to inhibiting or ameliorating the disease.

2. The method of claim 1 , wherein R 1 is C 1-6 alkyl.

3. The method of claim 1 , wherein R 1 is methyl.

4. The method of claim 1 , wherein R 2 , R 3 , R 4 , and R 5 are each independently selected from H, OH, CN, halo, C 1-4 alkyl, C 1-4 haloalkyl, and C 1-4 alkoxy.

5. The method of claim 1 , wherein Cy is aryl or heteroaryl, each substituted with m independently selected R C groups.

6. The method of claim 1 , wherein Cy is aryl, substituted with m independently selected R C groups.

7. The method of claim 1 , wherein Cy is phenyl, substituted with m independently selected R C groups.

8. The method of claim 1 , wherein each R C is independently selected from halo, CN, C 1-6 alkyl, C 1-6 haloalkyl, CN, OR a , C(O)R b , C(O)NR c R d , C(O)OR a , NR c R d , NR c C(O)R b , and S(O) 2 R b ; wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from hydroxy, C 1-6 alkoxy, and C 1-6 haloalkoxy.

9. The method of claim 1 , wherein each R C is independently halo or C 1-6 alkyl.

10. The method of claim 1 , wherein m is 1, 2, or 3.

11. The method of claim 1 , wherein Ar is

12. The method of claim 1 , wherein each R B is independently selected from methyl, amino, C 1-6 alkylamino, and di-C 1-6 -alkylamino.

13. The method of claim 1 , wherein n is 0.

14. The method of claim 1 , wherein R A is H.

15. The method of claim 1 , having Formula Ia:

or a pharmaceutically acceptable salt thereof.

16. The method of claim 1 , wherein the compound is a compound having Formula Ia-1:

or a pharmaceutically acceptable salt thereof.

17. The method of claim 1 , wherein the compound is a compound having Formula IIa, IIIb, or IVb:

or a pharmaceutically acceptable salt thereof.

18. The method of claim 1 , having Formula Ia-2:

or a pharmaceutically acceptable salt thereof.

19. The method of claim 1 , wherein the compound is a compound having Formula IIb, IIIb, or IVb:

or a pharmaceutically acceptable salt thereof.

20. The method of claim 1 , wherein the compound is a compound having Formula II, III, or IV:

or a pharmaceutically acceptable salt thereof.

21. The method of claim 1 , wherein:

Z is NR A ;

Cy is aryl or heteroaryl, each substituted with m independently selected R C groups; each R C is independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halosulfanyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halosulfanyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c R d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d ;

Ar is a purine ring, substituted with n independently selected R B groups;

R 1 is C 1-6 alkyl;

R A is selected from H and C 1-6 alkyl;

each R B is independently selected from C 1-6 alkyl and NR c1 R d1 R 1 ;

R 2 , R 3 , R 4 , and R 5 are each independently selected from H, OH, CN, halo, C 1-4 alkyl, C 1-4 haloalkyl, and C 1-4 alkoxy;

m is 1, 2 or 3; and

n is 0 or 1.

22. The method of claim 1 , wherein:

Z is NR A ;

Cy is aryl or heteroaryl, each substituted with m independently selected R C groups;

each R C is independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, CN, NO 2 , OR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d ; wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from hydroxy, C 1-6 alkoxy, and C 1-6 haloalkoxy;

Ar is a purine ring, substituted with n independently selected R B groups;

R 1 is C 1-6 alkyl;

R A is H or C 1-6 alkyl;

each R B is independently selected from C 1-6 alkyl and NR c1 R d1 ;

R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are each independently selected from H, halo, CN, C 1-6 alkyl, and C 1-6 haloalkyl;

m is 1, 2 or 3; and

n is 0 or 1.

23. The method of claim 1 , wherein:

Z is NR A ;

Cy is aryl, substituted with m independently selected R C groups;

each R C is independently selected from halo, CN, C 1-6 alkyl, C 1-6 haloalkyl, CN, OR a , C(O)R b , C(O)NR c R d , C(O)OR a , NR c R d , NR c C(O)R b , and S(O) 2 R b ; wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from hydroxy, C 1-6 alkoxy, and C 1-6 haloalkoxy;

Ar is a purine ring, substituted with n independently selected R B groups;

R A is H or C 1-6 alkyl;

each R B is independently selected from C 1-6 alkyl and NR c1 R d1 ;

R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are each independently selected from H, halo, CN, C 1-6 alkyl, and C 1-6 haloalkyl;

m is 1, 2 or 3; and

n is 0 or 1.

24. The method of claim 1 , wherein:

Z is NR A ;

Cy is phenyl, substituted with m independently selected R C groups;

each R C is independently halo or methyl;

R A is a moiety of formula:

R A is H;

each R B is independently selected from methyl and amino.

R 1 is independently selected from methyl;

R 2 , R 3 , R 4 , and R 5 are each independently selected from H, CN, F, Cl, methyl, ethyl, and trifluoromethyl;

m is 1, 2 or 3; and

n is 0 or 1.

25. The method of claim 1 , wherein the compound is selected from:

N-{1-[3-(3,5-Difluorophenyl)-5-methylimidazo[1,2-a]pyridin-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[3-(3-Fluorophenyl)imidazo[1,2-a]pyridin-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[5-(3,5-Difluorophenyl)imidazo[2,1-b][1,3]thiazol-6-yl]ethyl}-9H-purin-6-amine;

N-{1-[5-(3-Fluorophenyl)-3-methylimidazo[2,1-b][1,3]thiazol-6-yl]ethyl}-9H-purin-6-amine;

N-{1-[5-(3-Fluorophenyl)-2-methylimidazo[2,1-b][1,3]thiazol-6-yl]ethyl}-9H-purin-6-amine;

N-{1-[6-Chloro-3-(3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[5-Chloro-3-(3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[3-(3-Fluorophenyl)-6-methylimidazo[1,2-a]pyridin-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[3-(3-Fluorophenyl)-7-methylimidazo[1,2-a]pyridin-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[3-(3-Fluorophenyl)-8-methylimidazo[1,2-a]pyridin-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[8-Chloro-3-(3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[8-Ethyl-3-(3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[7-Chloro-3-(3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[8-Fluoro-3-(3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[3-(3-Fluorophenyl)-8-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]ethyl}-9H-purin-6-amine;

3-(3-Fluorophenyl)-2-[1-(9H-purin-6-ylamino)ethyl]imidazo[1,2-a]pyridine-8-carbonitrile;

N-{1-[3-(4-Methylphenyl)imidazo[1,2-a]pyridin-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[3-(2,3-Difluorophenyl)imidazo[1,2-a]pyridin-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[3-(2-Fluorophenyl)imidazo[1,2-a]pyridin-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[3-(2-Methylphenyl)imidazo[1,2-a]pyridin-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[3-(2,5-Difluorophenyl)imidazo[1,2-a]pyridin-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[3-(3-Methylphenyl)imidazo[1,2-a]pyridin-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[3-(3,5-Difluorophenyl)imidazo[1,2-a]pyridin-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[3-(4-Fluorophenyl)imidazo[1,2-a]pyridin-2-yl]ethyl}-9H-purin-6-amine; and

N-{1-[3-(3,5-Difluorophenyl)pyrazolo[1,5-a]pyridin-2-yl]ethyl}-9H-purin-6-amine;

or a pharmaceutically acceptable salt thereof.

26. The method of claim 1 , wherein said disease is breast cancer, prostate cancer, colon cancer, brain cancer, bladder cancer, skin cancer, cancer of the uterus, ovary cancer, lung cancer, pancreatic cancer, renal cancer, or gastric cancer.

27. The method of claim 1 , wherein said disease is acute myeloblastic leukemia, chronic myeloid leukemia, or B cell lymphoma.

28. The method of claim 1 , wherein said disease is B cell lymphoma.

29. The method of claim 1 , wherein the cancer of the uterus is endometrial cancer.

30. The method of claim 1 , wherein the compound is N-{1-[3-(3,5-difluorophenyl)-5-methylimidazo[1,2-a]pyridin-2-yl]ethyl}-9H-purin-6-amine, or a pharmaceutically acceptable salt thereof.

31. The method of claim 30 , wherein said disease is breast cancer, prostate cancer, colon cancer, brain cancer, bladder cancer, skin cancer, cancer of the uterus, ovary cancer, lung cancer, pancreatic cancer, renal cancer, or gastric cancer.

32. The method of claim 30 , wherein said disease is acute myeloblastic leukemia, chronic myeloid leukemia, or B cell lymphoma.

33. The method of claim 30 , wherein said disease is B cell lymphoma.

34. The method of claim 30 , wherein the cancer of the uterus is endometrial cancer.