Anticancer prodrug activated by radiation or ultraviolet treatment and use thereof

Patent metadata

Field	Value
Publication number	US-9408910-B2
Application number	US-201114001745-A
Country	US
Kind code	B2
Filing date	Mar 2, 2011
Priority date	Mar 2, 2011
Publication date	Aug 9, 2016
Grant date	Aug 9, 2016

Abstract

The present invention relates to an anticancer prodrug consisting of peptide of acetyl-SEQ ID NO: 1-linker-anticancer drug. The anticancer prodrug effectively provides an anticancer drug unstable in acid or base, such as doxorubicin, in a form of prodrug. Thus, the anticancer prodrug exists as a non-toxic inactive form when administered into the body, but effectively releases the anticancer drug as an active ingredient in the target area in the presence of caspase activated by radiation or UV treatment after administered into the body. Accordingly, the anticancer drug exhibits selective anticancer effects on cancer cells, thereby maximizing the therapeutic effect and minimizing the side-effects of chemotherapy.

First claim

What is claimed is:

1. An anticancer therapeutic kit, comprising:
a prodrug comprising (i) a peptide consisting of acetyl-SEQ ID NO: 1, (ii) a linker, and (iii) an anticancer drug that are sequentially linked to each other, wherein the linker is selected from the group consisting of para-aminobenzyloxycarbonyl, aminoethyl-N-methylcarbonyl, a dendritic linker and a cephalosporin-based linker; and
an apparatus for applying radiation to a subject at a dose between 1 Gy to 5 Gy or UV radiation at a dose between 1 J/m 2 to 50 J/m 2 UV so as to induce caspase activation in tumor cells in the subject.

2. The anticancer therapeutic kit of claim 1 , wherein the anticancer drug is selected from the group consisting of doxorubicin, paclitaxel, adriamycin, cisplatin, 5-fluorouracil, mitomycin, chlomomycin, bleomycin, peplomycin, daunorubicin, aclarrubicin, neocarzinostatin, epirubicin, idarubicin and pirarubicin.

3. The anticancer therapeutic kit of claim 1 , wherein the anticancer drug is doxorubicin, and the linker is para-aminobenzyloxycarbonyl.

4. The anticancer therapeutic kit according to claim 1 , wherein the apparatus is for radiation treatment at a dose of 1Gy to 5Gy.

5. The anticancer therapeutic kit according to claim 1 , wherein the apparatus is for UV radiation at a dose between 1 J/m 2 to 50 J/m 2 UV.

6. The anticancer therapeutic kit according to claim 1 , wherein the linker is selected from the group consisting of para-aminobenzyloxycarbonyl, aminoethyl-N-methylcarbonyl, aminobiphenylmethyloxycarbonyl, a dendritic linker and a cephalosporin-based linker.

7. The anticancer therapeutic kit according to claim 1 , wherein the linker is para-aminobenzyloxycarbonyl.

Assignees

• Ryu Ju-Hee
• Kim Kwang-Meyung
• Kwon Ick-Chan
• Choi Kui-Won
• Kim Sang-Yoon
• Lee Beom-Suk
• Chi Dae-Yoon
• Kil Hee-Seup
• Sung Hyun-Ju
• Korea Inst Sci & Tech

Inventors

• Ryu Ju-Hee
• Kim Kwang-Meyung
• Kwon Ick-Chan
• Choi Kui-Won
• Kim Sang-Yoon
• Lee Beom-Suk
• Chi Dae-Yoon
• Kil Hee-Seup
• Sung Hyun-Ju

Classifications

• A61N5/1001

  using radiation sources introduced into or applied onto the body; brachytherapy · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A61K41/0042 Primary

  Photocleavage of drugs in vivo, e.g. cleavage of photolabile linkers in vivo by UV radiation for releasing the pharmacologically-active agent from the administered agent; photothrombosis or photoocclusion · CPC title

• A61K31/704

  attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} · CPC title