Tsuyoshi Takara, Rei Takara, Aya Kobayashi, Hina Shirakata, Shinobu Ambai, Yusei Shinohara and Yoshihiro Uto : Serum-Derived Macrophage-Activating Factor ExhibitsAnti-Tumor Activity via M2-to-M1 Macrophage Reprogramming, International Journal of Translational Medicine, 4, 439-449, 2024.
Yusei Shinohara, Yuki Komiya, Kashin morimoto, Yoshio Endo, Minoru Terashima, Takeshi Suzuki, Takahisa Takino, Itasu Ninomiya, Hisatsugu Yamada and Yoshihiro Uto : Development of UTX-143, a Selective Sodium-hydrogen Exchange Subtype 5 Inhibitor, using Amiloride as a Lead Compound, Bioorganic & Medicinal Chemistry, 99, 117603, 2024.
(要約)
NHE5, an isoform of the Na/H exchanger (NHE) protein, is an ion-transporting membrane protein that regulates intracellular pH and is highly expressed in colorectal adenocarcinoma. Therefore, we hypothesized that NHE5 inhibitors can be used as anticancer drugs. However, because NHE1 is ubiquitously expressed in all cells, it is extremely important to demonstrate its selective inhibitory activity against NHE5. We used amiloride, an NHE non-selective inhibitor, as a lead compound and created UTX-143, which has NHE5-selective inhibitory activity, using a structure-activity relationship approach. UTX-143 showed selective cytotoxic effects on cancer cells and reduced the migratory and invasive abilities of cancer cells. These results suggest a new concept wherein drugs exhibit cancer-specific cytotoxic effects through selective inhibition of NHE5 and the possibility of UTX-143 as a lead NHE5-selective inhibitor.
Hirari Yamahana, Yusei Shinohara, Yoshio Endo, Tohru Obata, Hisatsugu Yamada and Yoshihiro Uto : Enhancing Effect of Novel Schiff Base Derivatives, UTX-134 and UTX-135, on 5-Aminolevulinic Acid-based Photodynamic Therapy, ALA-Porphyrin Science, 10, 1, 1-14, 2021.
(キーワード)
5-aminolevulinic acid / protoporphyrin IX / photodynamic therapy / shiff-base
4.
Yusei Shinohara, Yoshio Endo, Chiaki Abe, Ikkyu Shiba, Masahiro Ishizuka, Tohru Tanaka, Yutaka Yonemura, Syunichiro Ogura, Masahide Tominaga, Hisatsugu Yamada and Yoshihiro Uto : Development of a novel Schiff base derivative for enhancing the anticancer potential of 5-aminolevulinic acid-based photodynamic therapy., Photodiagnosis and Photodynamic Therapy, 20, 182-188, 2017.
(要約)
5-Aminolevulinic acid (ALA), a precursor of protoporphyrin IX (PpIX), is now widely used for photodynamic diagnosis (ALA-PDD) and photodynamic therapy (ALA-PDT) of various cancers. Recently, we found that treatment of cancer cells with the Schiff base derivative TX-816 along with ALA could significantly increase the efficacy of ALA-PDT. This enhancing effect of TX-816 on ALA-PDT is attributed to 3,5-dichlorosalicylaldehyde (DCSA), a molecule produced by the degradation of TX-816. Similar to TX-816, DCSA significantly enhances the effect of ALA-PDT. Furthermore, DCSA could restore the sensitivity of cancer cells that acquired resistance to ALA-PDT. These results indicate that DCSA, as well as TX-816, is a potent lead compound for the development of an ALA-PDT sensitizer. TX-816 might be a useful compound for designing prodrug-type ALA-PDT enhancers.
(キーワード)
5-Aminolevulinic acid / Photodynamic therapy / Protoporphyrin IX / Schiff base