Pharmaceutics 2011, 3(3), 615-635; doi:10.3390/pharmaceutics3030615
Review

Transporter-Mediated Drug Interaction Strategy for 5-Aminolevulinic Acid (ALA)-Based Photodynamic Diagnosis of Malignant Brain Tumor: Molecular Design of ABCG2 Inhibitors

1,* email, 2, 2, 2, 3, 3, 2 and 2
Received: 19 July 2011; in revised form: 16 August 2011 / Accepted: 9 September 2011 / Published: 14 September 2011
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Photodynamic diagnosis (PDD) is a practical tool currently used in surgical operation of aggressive brain tumors, such as glioblastoma. PDD is achieved by a photon-induced physicochemical reaction which is induced by excitation of protoporphyrin IX (PpIX) exposed to light. Fluorescence-guided gross-total resection has recently been developed in PDD, where 5-aminolevulinic acid (ALA) or its ester is administered as the precursor of PpIX. ALA induces the accumulation of PpIX, a natural photo-sensitizer, in cancer cells. Recent studies provide evidence that adenosine triphosphate (ATP)-binding cassette (ABC) transporter ABCG2 plays a pivotal role in regulating the cellular accumulation of porphyrins in cancer cells and thereby affects the efficacy of PDD. Protein kinase inhibitors are suggested to potentially enhance the PDD efficacy by blocking ABCG2-mediated porphyrin efflux from cancer cells. It is of great interest to develop potent ABCG2-inhibitors that can be applied to PDD for brain tumor therapy. This review article addresses a pivotal role of human ABC transporter ABCG2 in PDD as well as a new approach of quantitative structure-activity relationship (QSAR) analysis to design potent ABCG2-inhibitors.
Keywords: brain tumor; glioma; photodynamic diagnosis; 5-aminolevulinic acid (ALA); ABC transporter; ABCG2; protein kinase inhibitor
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MDPI and ACS Style

Ishikawa, T.; Takahashi, K.; Ikeda, N.; Kajimoto, Y.; Hagiya, Y.; Ogura, S.-I.; Miyatake, S.-I.; Kuroiwa, T. Transporter-Mediated Drug Interaction Strategy for 5-Aminolevulinic Acid (ALA)-Based Photodynamic Diagnosis of Malignant Brain Tumor: Molecular Design of ABCG2 Inhibitors. Pharmaceutics 2011, 3, 615-635.

AMA Style

Ishikawa T, Takahashi K, Ikeda N, Kajimoto Y, Hagiya Y, Ogura S-I, Miyatake S-I, Kuroiwa T. Transporter-Mediated Drug Interaction Strategy for 5-Aminolevulinic Acid (ALA)-Based Photodynamic Diagnosis of Malignant Brain Tumor: Molecular Design of ABCG2 Inhibitors. Pharmaceutics. 2011; 3(3):615-635.

Chicago/Turabian Style

Ishikawa, Toshihisa; Takahashi, Kenkichi; Ikeda, Naokado; Kajimoto, Yoshinaga; Hagiya, Yuichiro; Ogura, Shun-ichiro; Miyatake, Shin-ichi; Kuroiwa, Toshihiko. 2011. "Transporter-Mediated Drug Interaction Strategy for 5-Aminolevulinic Acid (ALA)-Based Photodynamic Diagnosis of Malignant Brain Tumor: Molecular Design of ABCG2 Inhibitors." Pharmaceutics 3, no. 3: 615-635.

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