Kinase-mediated trapping of bi-functional conjugates of paclitaxel or vinblastine with thymidine in cancer cells

被引：19

作者：

Aspland, Simon E. ^{[1
]}

Ballatore, Carlo ^{[1
]}

Castillo, Rosario ^{[1
]}

Desharnais, Joel ^{[1
]}

Eustaquio, Trisha ^{[1
]}

Goelet, Philip ^{[1
]}

Guo, Zijian ^{[1
]}

Li, Qing ^{[1
]}

Nelson, David ^{[1
]}

Sun, Chengzao ^{[1
]}

Castellino, Angelo J. ^{[1
]}

Newman, Michael J. ^{[1
]}

机构：

[1] Acidophil LLC, Lutherville Timonium, MD 21093 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 19期

关键词：

kinase-mediated trapping; thymidine kinase 1; thymidine; paclitaxel; vinblastine; fluorescein;

D O I：

10.1016/j.bmcl.2006.07.003

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In the present work, we explore the possibility of introducing selectivity to existing chernotherapeutics via the design of non-pro-drug, bi-functional molecules comprising a microtubule-binding agent and a substrate for a disease-associated kinase. The design, synthesis, and in vitro biological evaluation of paclitaxel thymidine and vinblastine-thymidine bi-functional conjugates are reported here. This work provides the first account of 'kinase-mediated trapping' of cancer therapeutics. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：5194 / 5198

页数：5

共 20 条

[1] Synthesis of a small library of 3-(Carboranylalkyl)thymidines and their biological evaluation as substrates for human thymidine kinases 1 and 2 [J].

Al-Madhoun, AS ;

Johnsamuel, J ;

Yan, JH ;

Ji, WH ;

Wang, JH ;

Zhuo, JC ;

Lunato, AJ ;

Woollard, JE ;

Hawk, AE ;

Cosquer, GY ;

Blue, TE ;

Eriksson, S ;

Tjarks, W .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (18) :4018-4028

[2] A facile route to paclitaxel C-10 carbamates [J].

Ballatore, C ;

Aspland, SE ;

Castillo, R ;

Desharnais, J ;

Eustaquio, T ;

Sun, SZ ;

Castellino, AJ ;

Smith, AB .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (10) :2477-2480

[3]

Buchmann I, 2004, CANCER BIOTHER RADIO, V19, P436

[4]

CASTELLINO AJ, Patent No. 20050148534

[5] Fluorescence-labeled sphingosines as substrates of sphingosine kinases 1 and 2 [J].

Ettmayer, P ;

Billich, A ;

Baumruker, T ;

Mechtcheriakova, D ;

Schmid, H ;

Nussbaumer, P .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (06) :1555-1558

[6] Thymidine kinase in epithelial ovarian cancer: Relationship with the other pyrimidine pathway enzymes [J].

Fujiwaki, R ;

Hata, K ;

Nakayama, K ;

Moriyama, M ;

Iwanari, O ;

Katabuchi, H ;

Okamura, H ;

Sakai, E ;

Miyazaki, K .

INTERNATIONAL JOURNAL OF CANCER, 2002, 99 (03) :328-335

[7] THYMIDINE KINASES - THE ENZYMES AND THEIR CLINICAL USEFULNESS [J].

HANNIGAN, BM ;

BARNETT, YA ;

ARMSTRONG, DBA ;

MCKELVEYMARTIN, VJ ;

MCKENNA, PG .

CANCER BIOTHERAPY, 1993, 8 (03) :189-197

[8]

Hengstschläger M, 1998, ADV EXP MED BIOL, V431, P455

[9] Recent advances in tumor-targeting anticancer drug conjugates [J].

Jaracz, S ;

Chen, J ;

Kuznetsova, LV ;

Ojima, L .

BIOORGANIC & MEDICINAL CHEMISTRY, 2005, 13 (17) :5043-5054

[10]

Kingston D G I, 2002, Fortschr Chem Org Naturst, V84, P53

← 1 2 →