Katsunori Takashima
Takeda Pharmaceutical Company
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Publication
Featured researches published by Katsunori Takashima.
British Journal of Pharmacology | 2009
Katsunori Takashima; Naoko Matsunaga; M Yoshimatsu; Kaoru Hazeki; Tsuneyasu Kaisho; M Uekata; Osamu Hazeki; Shizuo Akira; Yuji Iizawa
Background and purpose: TAK‐242, a novel synthetic small‐molecule, suppresses production of multiple cytokines by inhibiting Toll‐like receptor (TLR) 4 signalling. In this study, we investigated the target molecule of TAK‐242 and examined its therapeutic effect in a mouse sepsis model.
Antimicrobial Agents and Chemotherapy | 2005
Masanori Baba; Katsunori Takashima; Hiroshi Miyake; Naoyuki Kanzaki; Koichiro Teshima; Xin Wang; Mitsuru Shiraishi; Yuji Iizawa
ABSTRACT The first small-molecule CCR5 antagonist, TAK-779, could not be developed as an anti-human immunodeficiency virus type (anti-HIV-1) agent because of its poor oral bioavailability. TAK-652 is an orally bioavailable TAK-779 derivative with potent anti-HIV-1 activity. TAK-652 inhibited the binding of RANTES (regulated on activation, normal T-cell expressed and secreted), macrophage inflammatory protein 1α (MIP-1α), and MIP-1β to CCR5-expressing cells at nanomolar concentrations. TAK-652 could also suppress the binding of monocyte chemotactic protein 1 (MCP-1) to CCR2b-expressing cells. However, its inhibitory effect on ligand binding to other chemokine receptors was limited. TAK-652 was active against CCR5-using (R5) HIV-1 but totally inactive against CXCR4-using (X4) HIV-1. The compound was active against R5 HIV-1 clinical isolates containing reverse transcriptase and protease inhibitor-resistant mutations, with a mean 50% effective concentration (EC50) and EC90 of 0.061 and 0.25 nM, respectively. In addition, recombinant R5 viruses carrying different subtype (A to G) envelope proteins were equally susceptible to TAK-652. A single oral administration of TAK-652 up to 100 mg was safe and well tolerated in humans. The compound displayed favorable pharmacokinetics, and its plasma concentration was 7.2 ng/ml (9.1 nM) even 24 h after the administration of 25 mg. Thus, TAK-652 is a promising candidate as a novel entry inhibitor of HIV-1.
Antimicrobial Agents and Chemotherapy | 2005
Katsunori Takashima; Hiroshi Miyake; Naoyuki Kanzaki; Yoshihiko Tagawa; Xin Wang; Yoshihiro Sugihara; Yuji Iizawa; Masanori Baba
ABSTRACT TAK-220 is a member of a novel class of chemokine receptor antagonists and is highly specific to CCR5, as determined by receptor binding and calcium mobilization assays. The compound selectively inhibited coreceptor-mediated entry of human immunodeficiency virus type 1 (HIV-1) into host cells and HIV-1 infection mediated by CCR5. TAK-220 inhibited the replication of six CCR5-using (R5) HIV-1 clinical isolates in peripheral blood mononuclear cells (PBMCs) with a mean 90% effective concentration of 13 nM. The anti-HIV-1 activity of TAK-220 was not affected by addition of high concentrations of human serum. It equally inhibited R5 HIV-1 replication in PBMCs obtained from eight different donors, irrespective of the levels of viral production. Furthermore, the anti-HIV-1 activity of TAK-220 was found to be subtype independent. TAK-220 did not induce CCR5 internalization but blocked the binding of two monoclonal antibodies that recognize the second extracellular loop of CCR5 in CCR5-expressing cells. These results suggest that TAK-220 selectively inhibits R5 HIV-1 replication by interfering with coreceptor-mediated entry of the virus into host cells. At a dose of 5 mg/kg of body weight, TAK-220 showed oral bioavailabilities of 9.5 and 28.9% in rats and monkeys, respectively. Thus, TAK-220 is a promising candidate for the treatment of HIV-1 infection.
Molecular Pharmacology | 2006
Masayuki; Naoko Matsunaga; Kaoru Hazeki; Kazuyo Nakamura; Katsunori Takashima; Tsukasa Seya; Osamu Hazeki; Tomoyuki Kitazaki; Yuji Iizawa
Journal of Medicinal Chemistry | 2006
Masaki Seto; Katsuji Aikawa; Naoki Miyamoto; Yoshio Aramaki; Naoyuki Kanzaki; Katsunori Takashima; Yoji Kuze; Yuji Iizawa; Masanori Baba; Mitsuru Shiraishi
Journal of Medicinal Chemistry | 2006
Shinichi Imamura; Takashi Ichikawa; Youichi Nishikawa; Naoyuki Kanzaki; Katsunori Takashima; Shin-Ichi Niwa; Yuji Iizawa; Masanori Baba; Yoshihiro Sugihara
Inflammation Research | 2010
Hiroyuki Seki; Sadatomo Tasaka; Koichi Fukunaga; Yoshiki Shiraishi; Kiyoshi Moriyama; Keisuke Miyamoto; Yasushi Nakano; Naoko Matsunaga; Katsunori Takashima; Tatsumi Matsumoto; Masayuki; Akitoshi Ishizaka; Junzo Takeda
Archive | 2006
Masayuki; Naoko Matsunaga; Kaoru Hazeki; Kazuyo Nakamura; Katsunori Takashima; Tsukasa Seya; Osamu Hazeki; Tomoyuki Kitazaki; Yuji Iizawa
Archive | 2005
Masayuki; Naoko Matsunaga; Kaoru Hazeki; Kazuyo Nakamura; Katsunori Takashima; Tsukasa Seya; Osamu Hazeki; Tomoyuki Kitazaki; Yuji Iizawa
Critical Care Medicine | 2004
Masayuki; Mie Sunamoto; Naoko Matsunaga; Kazuyo Nakamura; Katsunori Takashima; Tomoyuki Kitazaki; Yuji Iizawa; Jun Sato