Compound for inhibition of delta-5-desaturase (D5D) and treatment of cancer and inflammation
Tricyclic compounds, including tricyclic iminodibenzylic and tricyclic iminostilbene compounds, are identified as therapeutic agents for inhibition of delta-5-desaturase (D5D) and for treating or preventing cancer and precancerous conditions, as well as autoimmune and inflammatory conditions. Pharmaceutical compositions and dietary supplements are provided, as are methods of administration and treatment.
1. A method for treating or preventing cancer or a precancerous condition in a subject, the method comprising administering to the subject a composition comprising an effective amount of a compound, wherein the subject is afflicted with or at risk of having a cancer characterized by high COX-2 expression, wherein the compound is an iminodibenzyl or a derivative thereof, wherein the iminodibenzyl has the formula:
wherein the derivative is a disubstituted or monosubstituted derivative having formula (Ia):
wherein R 1 and R 2 are each independently selected from H, (C1-C6) alkyl, hydroxy, alkoxy, aminoalkyl, halo, or haloalkyl provided that at least one of R 1 and R 2 is not H.
2. The method of claim 1 , wherein the cancer is a cancer of the colon, rectum, breast, prostate, liver, pancreas, bone, brain, ovary, cervix, larynx, lung, esophagus, testicle, skin, spine, stomach, bladder, kidney, uterus, thyroid, blood or immune system.
3. A method for inhibiting the growth of a tumor in a subject, the method comprising:
administering to the subject a composition comprising an effective amount a compound, wherein the subject is afflicted with a tumor characterized by high COX-2 expression, wherein the compound is an iminodibenzyl or a derivative thereof, wherein the iminodibenzyl has the formula:
wherein the derivative is a disubstituted or monosubstituted derivative having formula (Ia):
wherein R 1 and R 2 are each independently selected from H, (C1-C6) alkyl, hydroxy, alkoxy, aminoalkyl, halo, or haloalkyl provided that at least one of R 1 and R 2 is not H.
4. The method of claim 3 , wherein the tumor comprises a solid tumor disposed in the colon, rectum, breast, prostate, liver, pancreas, bone, brain, ovary, cervix, larynx, lung, esophagus, testicle, skin, spine, stomach, bladder, kidney, uterus, thyroid, or immune system of the subject.
5. A method for treating or preventing cancer metastasis, migration, or invasion in a subject, the method comprising administering to the subject a composition comprising an effective amount of a compound, wherein the subject is afflicted with or at risk of having a cancer metastasis, migration, or invasion characterized by high COX-2 expression, wherein the compound is an iminodibenzyl or a derivative thereof, wherein the iminodibenzyl has the formula:
wherein the derivative is a disubstituted or monosubstituted derivative having formula (Ia):
wherein R 1 and R 2 are each independently selected from H, (C1-C6) alkyl, hydroxy, alkoxy, aminoalkyl, halo, or haloalkyl provided that at least one of R 1 and R 2 is not H.
6. The method of claim 5 , wherein the cancer is a cancer of the colon, rectum, breast, prostate, liver, pancreas, bone, brain, ovary, cervix, larynx, lung, esophagus, testicle, skin, spine, stomach, bladder, kidney, uterus, thyroid, blood or immune system.
7. A method for treating or preventing cancer or a precancerous condition in a subject, inhibiting the growth of a tumor in a subject, or treating or preventing cancer metastasis, migration, or invasion in a subject, the method comprising
providing a kit comprising a compound, wherein the compound is an iminodibenzyl or a derivative thereof, wherein the iminodibenzyl has the formula:
wherein the derivative is a disubstituted or monosubstituted derivative having formula (Ia):
wherein R 1 and R 2 are each independently selected from H, (C1-C6) alkyl, hydroxy, alkoxy, aminoalkyl, halo, or haloalkyl provided that at least one of R 1 and R 2 is not H; and
providing a label that comprises instructions for a dosage regimen comprising dosing amount, frequency of dosing, or a combination thereof, wherein the subject is afflicted with or at risk of having a cancer characterized by high COX-2 expression, is afflicted with a tumor characterized by high COX-2 expression, or is afflicted with or at risk of having a cancer metastasis, migration, or invasion characterized by high COX-2 expression.
8. The method of claim 2 , wherein the cancer is colorectal cancer.
9. The method of claim 2 , wherein the subject has a risk factor for developing cancer or a precancerous condition, and wherein the compound is administered prior to the development of a cancer or precancerous condition.
10. The method of claim 2 wherein the subject is afflicted with a cancer that is therapy-refractory.
11. The method of claim 1 , wherein R 1 and R 2 are each independently selected from H, —CH 3 , —OCH 3 , —OH, —CH(CH 3 ) 2 , —C(CH 3 ) 3 , —N(CH 3 ) 2 , —F or —CF 3 , provided that at least one of R 1 and R 2 is not H.
12. The method of claim 1 , wherein R 1 and R 2 are positioned at the (1, 9) ring positions, the (3, 7) ring positions, or the (4, 6) ring positions.
13. The method of claim 1 , wherein R 1 and R 2 are positioned at the (1, 9) ring positions.
14. The method of claim 1 , wherein R 1 is H and R 2 is positioned at the 1, 2, 3, or 4 ring position.
15. The method of claim 1 , wherein R 1 is H and R 2 is positioned at the 1 ring position.
16. The method of claim 1 , wherein the derivative has a (10, 11)-dihydro dibenzazepine moiety.
17. The compound of claim 1 , wherein the derivative has a dibenzazepine moiety.
18. The method of claim 1 , wherein R 1 =R 2 .
19. The compound of claim 1 , wherein R 1 ≠R 2 .