Compositions and methods for treating cancer

1. A protected anti-neoplastic agent of the formula Hyp-N, wherein

Hyp is a hypoxic activator having the formula:

wherein R 1 is C 1 -C 6 alkyl or C 1 -C 6 alkoxy;

R 2 is hydrogen;

R 3 is —H or C 1 -C 6 alkyl; and

R 4 is —H, C 1 -C 6 alkyl, or C 1 -C 6 alkoxy;

and N is an anti-neoplastic agent, wherein the anti-neoplastic agent is selected from the group consisting of doxorubicin, daunorubicin, duocarmycin, etoposide, duetoposide, Combretastatin A-4, vinblastine, vincristine, camptothecin, topotecan, 5-fluorouracil, AQ4N, hydroxyurea, maytansines, enediyenes, discodermolides, epothilones, taxanes, calicheamicins, tedanolides, bleomycins, calicheamicins, colchicine, cytarabine, dacarbazine, dactinomycin, discodermolides, epirubicin, fludarabine, hydroxyureapentostatin, 6-mercaptopurine, methotrexate, mitomycin, mitoxantrone, carboplatin, cisplatin, prednisone, procarbazine, taxanes, docetaxel, paclitaxel, tedanolides, teniposide, 6-thioguanine, vinca alkaloids, cyclophosphamides, platinum coordination complexes, anthracenediones, and an alkylating agent; and N is bonded to Hyp by an —O— group in N.

2. The protected anti-neoplastic agent of claim 1 , wherein the anti-neoplastic agent is an alkylating agent.

3. The protected anti-neoplastic agent of claim 2 , wherein the anti-neoplastic agent is a nitrogen mustard agent.

4. The protected anti-neoplastic agent of claim 1 , wherein R 1 is methyl.

5. The protected anti-neoplastic agent of claim 1 , wherein the anti-neoplastic agent has an IC 50 of less than 100 nM.

6. The protected anti-neoplastic agent of claim 1 , wherein the anti-neoplastic agent is selected from the group consisting of daunorubicin and camptothecin.

7. The protected anti-neoplastic agent of claim 1 of the formula:

8. A composition for treating cancer comprising a therapeutically effective amount of a protected anti-neoplastic agent of claim 2 .

9. The composition of claim 1 , wherein the cancer is selected from the group consisting of colon cancer, prostate cancer, lung cancer, non-small cell lung cancer, liver cancer, skin cancer, sarcomas, pancreatic cancer, breast cancer, head and neck cancer, and myeloma.

10. A method of treating colon cancer comprising administering a protected anti-neoplastic agent according to claim 1 wherein the anti-neoplastic agent is daunorubicin to a subject in need thereof.

11. The protected anti-neoplastic agent of claim 1 , wherein the alkylating agent is selected from the group consisting of cyclophosphamide, ifosfamide, melphalan, chlorambucil, and thiotepa.