Bioorganic Chemistry, Medicinal Chemistry, Drug Delivery Science
Subject of Study
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Book / Paper
Academic Paper (Judged Full Paper):
1.
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, Vol.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, Vol.99, 117603, 2024.
(Summary)
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.