著者

長谷川 宏之

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.52, no.3, pp.243-245, 2016 (Released:2016-03-01)

参考文献数

9

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バイオベンチャーの盛り上がりムードは2004年頃にピークを迎えたが、バイオベンチャーは2005年頃からの株式市場での上場バイオベンチャーに対する評価見直し,ライブドア事件に端を発した新興株式市場への不信感による株価下落および世界金融危機により厳しい時代を経験した.その後,2012年の山中伸弥博士によるノーベル賞受賞,アベノミクスによるライフサイエンス分野に対する各種施策等から,最近はその盛り上がりを戻しつつある.薬学・製薬企業出身のベンチャーキャピタリストが、大学発バイオベンチャーに対する投資検討する上でどのような観点でその技術・事業を見ているのかを紹介した.

著者

服部 友紀子

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.52, no.3, pp.258, 2016 (Released:2016-03-01)

参考文献数

3

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エリスロポエチンは,エリスロポエチン感受性を有する後期赤芽球系前駆細胞に作用し赤血球産生を促進する.しかし,溶血や敗血症,遺伝的骨髄不全疾患などの貧血患者においてはこの応答性が十分でなく,エリスロポエチン治療に抵抗性を示す.したがって,このような貧血の治療には,同じく赤血球産生増加作用を有するグルココルチコイドが用いられる.しかし,グルココルチコイドは骨粗しょう症,肥満,高血圧,糖尿病といった様々な副作用を誘発することから,患者の生活の質を高められるよりよい治療法の確立は早急な課題である.本稿では,核内受容体であるペルオキシソーム増殖活性化受容体α(peroxisome proliferator-activated receptor α:PPARα)の活性化がグルココルチコイド依存的な赤血球産生を促進することを見いだし,エリスロポエチン抵抗性貧血に対する新たな治療法となる可能性を示したLeeらの報告について紹介する.なお、本稿は下記の文献に基づいて、その研究成果を紹介するものである。1) Wessely O. et al., EMBO. J., 16, 267-280 (1997).2) Lee H. Y. et al., Nature, 522, 474-477 (2015).3) Flygare J. et al., Blood, 117, 3435-3444 (2011).

著者

味澤 幸義 赤羽 健司 赤羽 増夫 佐藤 和明 玉井 哲郎 斉藤 勝 田中 信之 鎌田 晃爾 小林 通洋

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.116, no.9, pp.735-747, 1996-09-25 (Released:2008-05-30)

参考文献数

13

被引用文献数

1 1

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A number of benzimidazole derivatives were synthesized and tested for cholecystokinin A (CCK-A) receptor inhibitory activity in order to study structure-activity relationships. Significant CCK-A receptor inhibitory activities were found in the compounds having carboxyl or tetrazolyl group. As the most preferred compound, 4-(5, 6-dichlorobenzimidazol-2-yl)-N-(3-methoxypropyl)-N-pentylglutaramic acid (4g) was selected.

著者

小林 義典

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.50, no.1, pp.7_2, 2014 (Released:2016-02-01)

著者

田中 洋和 中原 邦夫 畑中 洋 稲村 典昭 黒田 昭雄

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.117, no.8, pp.542-554, 1997-08-25 (Released:2008-05-30)

参考文献数

17

被引用文献数

7 19

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Tacrolimus hydrate (FK506), a novel 23-membered macrolide, is an immunosuppressant isolated from Streptomyces tsukubaensis using extensive screening of fermentation products to identify a compound inhibiting the mixed lymphocyte reaction (MLR). The in vitro and in vivo immunosuppressive activities of FK506 were found to be more potent than those of cyclosporine (CyA). The superior immunosuppression with FK506 treatment was also confirmed in the skin allograft model in rats and liver transplantation in dogs. Clinical studies were initiated by Prof. Starzl at the University of Pittsburgh in 1989, and he demonstrated that FK506 surpassed CyA in the incidence of graft survival and the frequency of graft rejection. Multicenter randomized clinical studies, comparing FK506 to CyA corroborated the efficacy of FK506 on the survival of patients and of grafts, and especially on the appearance of severe refractory graft rejection. FK506 was marketed in 1993 in Japan, and was followed in 1994 in the U.S.A., U.K, and Germany. The mechanism of action of this compound was clarified by the endeavors of Prof. Schreiber, who demonstrated the existence of a binding protein for FK506 called FKBP, similar to cyclophilin for CyA. The FK506/FKBP complex binds with calcineurin, a serine/threonine phosphatase to inhibit the translocation of NFAT into the nucleus, resulting in inhibition of transcription of IL-2 mRNA. FK506 displays potent immunosuppressant activity, and contributes not only to the progress of transplantation therapy for clinical studies, but also to the clarification of signal transduction in T cell activation for basic science.

著者

長尾 康次 上田 聡 神田 宗和 大畑 暢敬 山下 道雄 日野 資弘

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.130, no.11, pp.1471-1478, 2010 (Released:2010-11-01)

参考文献数

10

被引用文献数

2 2

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Natural fermentation products have long been studied as attractive targets for drug discovery due to their amazing diverse, complex chemical structures and biological activities. As such, a number of revolutionary drugs developed from natural fermentation products have contributed to global human health. To commercialize a drug derived from natural fermentation products, an effective chemical entity must be identified and thoroughly researched, and an effective manufacturing process to prepare a commercial supply must be developed. To construct such a manufacturing process for tacrolimus and micafungin, the following studies were conducted: first, we focused on controlling the production of the tacrolimus-related compound FR900525, a fermentation by-product of tacrolimus which was critical for quality assurance of the drug substance. FR900525 production was reduced by using a mutant strain which produced more pipecolic acid, the biosynthesis material of tacrolimus, than the original strain. Then, to optimize the fermentation process of FR901379, an intermediate of micafungin, a fed-batch culture was adopted to increase FR901379 productivity. Additionally, FULLZONETM impeller was installed into the scaled-up fermenter, reducing the agitation-induced damage to the mycelium. As a result, the mycelial form changed from filamentous to pellet-shaped, and the air uptake rate during fermentation was drastically improved. Finally, we conducted screening for FR901379 acylase-producing microorganisms, as FR901379 acylase is necessary to manufacture micafungin. We were able to easily discover FR901379 acylase-producing microorganisms in soil samples using our novel, convenient screening method, which involves comparing the difference in antibiotic activity between FR901379 and its deacylated product.

著者

荒田 洋治

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア

巻号頁・発行日

vol.48, no.6, pp.538-538_1, 2012

著者

長尾 善光

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.102, no.5, pp.401-427, 1982-05-25 (Released:2008-05-30)

参考文献数

55

被引用文献数

3 4

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The auther has developed numerous new reactions utilizing sulfur-containing leaving groups and attempted to use them for the synthesis of biologically active natural products. As shown in Chart 2, the mode of elimination of the sulfur-containing leaving groups is classified into two types. In the first half of this review, a type 2 reaction, in which 3-acyl-1, 3-thiazolidine-2-thione is used as Y-[○!S]and an amine as the nucleophile, is outlined. In the latter half, its application is described. It is concerned with the total synthesis of macrocyclic spermidine alkaloids (codonocarpine, (±)-lunarine, and (±)-lunaridine), the peptide synthesis, the total synthesis of parabactin, a spermidine-containing siderophore, the synthesis of new hypoxic cell sensitizers, FNT-1 and FNT-2, and a new design for chiral induction to the prochiral a cyclic molecules.

著者

土谷 義己 森 昌斗 田口 胤三

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.96, no.4, pp.490-497, 1976-04-25 (Released:2008-05-30)

参考文献数

24

被引用文献数

3 5

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To examine the effect of neighboring group on thermal treatment of O-alkyl S-methyl dithiocarbonates, syntheses of O-ethyl S-methyl dithiocarbonates holding alkyl (or aryl)-sulfinyl group were tried by the reaction of 2-alkyl (or aryl) sulfinylethanol and carbon disulfide in an aqueous sodium hydroxide followed by methylation with methyl iodide. However, the reaction did not progress as expected and gave 2-alkyl (or aryl) sulfinylethyl methyl trithiocarbonates (Va, -d) as main products. Nuclear magnetic resonance spectral data of these products suggested the formation of trithiocarbonate to occur via elimination and addition. It was thereby clarified that the alkyl (or aryl) sulfinyl as the neighboring group worked as an electron-attracting group to favor elimination.

著者

奥住 竜哉

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.52, no.3, pp.204, 2016 (Released:2016-03-01)

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最近,“バランス感覚”について考えることが多くなった.「あの人はバランス感覚いいよね」「あの人はバランス感覚に欠けるよね」など,日常会話でしばしば使う言葉である.感覚的に理解しているつもりになっているが,解釈は意外と難しい.“バランス感覚”とはどんな意味だろうか? 改めて考えてみると,「相反する2つの指標の間で,状況に応じて適切なポジションを取る力」のように思う.仕事をする中で,正反対のことがいずれも大事であるということは往々にしてある.例えば,大胆さと慎重さ,攻めと守り,安定と変化など挙げればきりがない.これら2つの正反対の指標の間で,置かれた状況を踏まえて適切なポジションをとって物事を進めていける力,が“バランス感覚”なのではないだろうか.「慎重かつ大胆に進めてくれ」と言われたら普通の人は面食らうだろうが,そこで落ち着いて状況を分析して適切な行動を起こせる人は,バランス感覚に優れた人と言える.考えてみれば仕事とは矛盾の塊である.企業の例で言えば,端的なのが「利益を上げる」という言葉だ.利益を上げるためには,売上を増やしてコストを減らすことが必要であるが,一般に売上を増やすにはコストがかかるからである.したがって,利益を最大化しようとすると「売上とコスト」という2つの相反する指標の間で適切なポジショニングを取る必要があるわけである.仕事の本質とは,このような矛盾する2つの指標の間で適切なポジションを取り,課題を解決することだと考えれば,バランス感覚という能力は仕事をする上で必要不可欠な能力と言える.

著者

道中 康也

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア

巻号頁・発行日

vol.52, no.6, pp.549-551, 2016

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一般名:オキシブチニン塩酸塩<br>薬価収載日(西暦表記):2013 年 5 月 24 日<br>過活動膀胱治療で永らく使用されているオキシブチニン塩酸塩を主薬とする経皮吸収型製剤ネオキシテープを開発した。オキシブチニンの経皮吸収性を高めるため、適度な薬物溶解性をもつゴム系基剤を選択した。さらに伸縮性を有する支持体を採用することで、良好な付着性を確保している。本剤を用いた比較臨床試験により、抗コリン性副作用である口内乾燥と便秘の発現率はプロピベリン経口投与群よりも低値であることが示された。

著者

栗秋 要

出版者

公益社団法人 日本薬学会

雑誌

藥學雜誌

巻号頁・発行日

vol.64, no.2, pp.128-129, 1944

著者

大沢 基保

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.129, no.3, pp.305-319, 2009 (Released:2009-03-01)

参考文献数

58

被引用文献数

17 25

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Immunotoxic effects of heavy metals, as a typical environmental agent, and their mechanisms are reviewed based on our findings on autoimmune response induced by exposure to cadmium (Cd) as CdCl2. Adverse immune effects of chemicals, defined as immunotoxicity, have been used as a sensitive biomarker for assessing health effects of environmental chemicals. My initial research focused on renal toxicity of heavy metals was developed to elucidate characteristics and mechanisms for immune-mediated nephritis induced by heavy metals. In our studies the most interesting finding was autoantibody production enhanced by the oral exposure to Cd at environmental levels. It was observed simultaneously with enhancement of non-specific antibody production and suppression of primed-antigen specific antibody production. Immunostimulation including induction of autoantibodies was found to be the primary immunotoxic effect of Cd, because of the dose-sensitivity, and to be associated with polyclonal B cell activation (PBA). Further mechanism studies on the PBA induced by Cd in vitro showed that it was mediated by T cells, via cytokines, dominantly Type-2 cytokines, and recognition of MHC-II antigens of cell surface. The similarity among PBAs induced by inorganic salts of Cd, mercury and lead suggests that it would be the common effect among the metals to be involved in their pathogenesis of nephritis. Finally possible health significance of chemical-induced PBA is discussed associated with an increasing trend of autoimmune diseases in industrialized countries.

著者

吉田 稔

出版者

公益社団法人 日本薬学会

雑誌

衛生化学 (ISSN:0013273X)

巻号頁・発行日

vol.44, no.3, pp.168-181, 1998-06-30 (Released:2008-05-30)

参考文献数

82

被引用文献数

3 4

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Mercury exists as elemental mercury (liquid mercury or mercury vapor), inorganic mercury salts (mercurous or mercuric), and organic mercury compounds (aryl- or alkylmercury). Due to the different chemical and physiological properties of all forms of mercury the effects of mercury on humans shows quite different clinical pictures. In this paper, mercury vapor and inorganic mercury poisoning are mainly reviewed. Liquid mercury, since it is poorly absorbed from the gastrointestinal tract, is nontoxic. Mercury vapor (Hg0) is absorbed rapidly from the alveolar membrane by inhalation and is accumulated mainly in the brain and kidney. In acute exposure to high concentrations of mercury vapor, the symptoms of respiratory, such as chest pain, cough, hemoptysis, and interstitial pneumonitis occur shortly after inhalation. In chronic exposure to relatively low concentrations of mercury vapor, neurological changes are prominent. The signs and symptoms of mercury vapor poisoning is characterized by gingivitis, intentional tremor and erethism, and in addition, weakness, fatigue, loss of weight, and disturbance of gastrointestinal functions appear unspecifically. Effects of inorganic mercury toxicity manifest in the gastrointestinal tract and kidney after ingestion. Early signs and symptoms appear as pharyngitis, dysphagia, abdominal pain, nausea and vomiting, and bloody diarrhea. Afterward renal failure due to necrosis of the proximal tubular epithelium occurs and develops into anuria and uremia. The occurrences of mercury vapor poisoning due to occupational or accidental exposures and inorganic mercury poisoning due to accidental or suicidal ingestion are reducing today in Japan.

著者

Sandoval Moises Burgos Johanna Sepulveda Francisco V. Cid L. Pablo

出版者

公益社団法人 日本薬学会

雑誌

Biological & Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.34, no.6, pp.803-809, 2011

被引用文献数

10

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The importance of intracellular pH (pH_i) in the regulation of diverse cellular activities ranging from cell proliferation and differentiation to cell cycle, migration and apoptosis has long been recognised. More recently, extracellular pH (pH_o), in particular that of relatively inaccessible compartments or domains that occur between cells in tissues, has begun to be acknowledged as a relevant signal in cell regulation. This should not be surprising given the abundant reports highlighting the pH_o-dependence of the activity of membrane proteins facing the extracellular space such as receptors, transporters, ion channels and enzymes. Changes in pH affect the ionisation state of proteins through the effect on their titratable groups. There are proteins, however, which respond to pH shifts with conformational changes that are crucial for catalysis or transport activity. In such cases protons act as signalling molecules capable of eliciting fast and localised responses. We provide examples of ion channels that appear fastidiously designed to respond to extracellular pH in a manner that suggests specific functions in transporting epithelia. We shall also present ideas as to how these channels participate in complex transepithelial transport processes and provide preliminary experiments illustrating a new way to gauge pH_o in confined spaces of native epithelial tissue.

著者

永倉 正彦 岡本 敏彦

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.92, no.2, pp.167-175, 1972-02-25 (Released:2008-05-30)

参考文献数

15

被引用文献数

1 1

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An addition-elimination reaction, which was reported in the reaction of 3-nitroquinoline with aqueous sodium hypobromite in methanolic KOH, also occurred in the case of other nitroquinolines, i.e., 6-, 5-, 8-, and 4-nitroquinolines. 6-Nitroquinoline (I) gave 6-bromo-5-methoxyquinoline (IIa), 6, 8-dibromo-5-methoxyquinoline (IIb), 6-bromo-5, 7-dimethoxyquinoline (IIIa), 5, 7-dimethoxy-6-nitroquinoline (IIIb), 8-bromo-5, 7-dimethoxy-6-nitroquinoline (IIIc), and 8-bromo-6-oxo-5, 5, 7-trimethoxy-5, 6-dihydroquinoline (IV) on being reacted in the same way as in the reaction of 3-nitroquinoline. Other nitroquinolines and their products from the same reaction were ; 5-nitroquinoline (XI); 5-bromo-6-methoxyquinoline (XIIa), 6-methoxy-5-nitroquinoline (XIIb), 8-methoxy-5-nitroquinoline (XIIIa), 5, 7-dibromo-6, 8-dimethoxyquinoline (XIVa), and 6, 8-dimethoxy-5-nitroquinoline (XIVb). 8-Nitroquinoline (XVIII); 8-bromo-7-methoxyquinoline (XIX), 5-methoxy-8-nitroqninoline (XX), and 6-bromo-5, 7-dimethoxy-8-nitroquinoline (XXI). 4-Nitroquinoline (XXII); 4-bromo-3-methoxyquinoline (XXIIIa), 3-methoxy-4-nitroquinoline (XXIIIb), 2, 3-dimethoxy-4-nitroquinoline (XXIV) and 4-methoxyquinoline (XXV). The reaction of 2-nitroquinoline (XXX) gave only 2-methoxyquinoline (XXXI).

著者

横尾 信夫 服部 英三 平田 光輝 渡辺 好一郎 佐藤 文泰 永倉 正彦 藤井 節郎

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.107, no.9, pp.732-737, 1987-09-25 (Released:2008-05-30)

参考文献数

9

被引用文献数

1 1

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Synthesis of water-soluble chymotrypsin specific inhibitors was attempted to study the roles of chymotrypsin-like enzymes in vivo. Previously we reported that the esters of carboxylic acid containing a condensed ring showed stronger activity than those containing a single ring system. Then we synthesized 4-substituted phenyl esters of carboxylic acid containing a condensed ring, such as tetralin, naphthalene, indole etc., and their inhibitory activities were compared. Among these compounds, esters of tetralin-1-carboxylic acid (FK-448) and 1-naphthylacetic acid showed the strongest activity, and their IC50 values were 8×10-7, 5×10-7 M, respectively. Tetralin-2-carboxylate and 2-naphthylacetate inhibited weaker than 1-analogues. Esters of basic quinoline carboxylic acid and bulky carboxylic acids containing a three-ring system inhibited poorly. Chymotrypsin produced equimolecular 4-substituted phenol rapidly and thereafter the amount of 4-substituded phenol increased slowly, when incubated with FK-448 at 37°C.

著者

薬師寺 文華

出版者

公益社団法人 日本薬学会

雑誌

MEDCHEM NEWS

巻号頁・発行日

vol.26, no.3, pp.121-124, 2016

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<p>米国ボストンにあるハーバード大学、Broad Institute of Harvard and MITのStuart L. Schreiber教授が主宰する研究室に2年間留学する機会を得た。Schreiber研究室は、現在Broad Instituteの3階にあり、大学研究室の枠を越えた大規模な研究展開を行っている。最近では、ガン細胞における遺伝子発現と低分子化合物に対する感受性との間に相関を見出すことで、化合物の作用機構を考察する計算科学的手法を発表している。Schreiber教授の研究例を含め、大規模データ解析による知見の構築が次世代創薬の流れをつくりつつある。実際にBroad InstituteはGoogle genomicsと提携し、ゲノム解析ソフトGATKをGoogleクラウドプラットフォーム上で使用できるサービスを開始しており、生物医学や創薬研究に与えるインパクトの大きさがうかがえる。Schreiber研究室への留学という好機に恵まれたことに深く感謝し、今後も幅広い研究活動を行えるよう努力を重ねていきたい。</p>

著者

津田 恭介

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.69, no.11, pp.486-488, 1949-11-25 (Released:2010-02-19)

参考文献数

15

著者

鈴木 順子 今津 嘉宏

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.138, no.5, pp.599-600, 2018 (Released:2018-05-01)