著者
中原 拓
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.58, no.11, pp.1070-1071, 2022 (Released:2022-11-01)
参考文献数
12

メタジェンセラピューティクスは、腸内細菌を活用した医療の社会実装と創薬を目指すバイオベンチャーである。順天堂大学で8年間積み重ねられた腸内細菌叢移植療法(FMT)を基盤として、潰瘍性大腸炎などを対象とした創薬を進める。FMT臨床研究を起点として、創薬シーズと有効性エビデンスを短期間で獲得し、最先端の微生物学・バイオインフォマティクスを活用したリバーストランスレーショナル創薬を推進する。
著者
辰巳 圭太
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.56, no.6, pp.554-555, 2020 (Released:2020-06-01)
参考文献数
4

ニュベクオ錠は、極性基を有するピラゾール環など、従来とは異なる特徴的な化学構造を有する非ステロイド性抗アンドロゲン剤である。また、非臨床薬物動態試験ではマウスにおいて脳内への移行性が低いことが示されている。本剤は、ハイリスクの非転移性去勢抵抗性前立腺癌患者を対象とした第Ⅲ相臨床試験において有効性と安全性が示された。我が国では、2020年1月に「遠隔転移を有しない去勢抵抗性前立腺癌」の効能・効果にて承認を取得し、2020年4月に薬価収載された。
著者
比留間 航 駿河 康平 門倉 一成 富田 剛 関野 芳弘 小松 靖弘 木村 公彦 小野 信文
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.133, no.5, pp.487-491, 2013-05-01 (Released:2013-05-01)
参考文献数
14
被引用文献数
5 5

Cancer is the most common cause of death in Japan. Fundamental and clinical studies on cancer were conducted from the viewpoint of Western medicine so far. However, a sustained complete remission has not been achieved yet. In order to alleviate the side effects of anticancer drugs, some traditional herbal medicines (Kampo medicines) have been prescribed to cancer patients. We have been studying on antitumor substances in medicinal herbs and found an antitumor medicinal herb named Rhus verniciflua (lacquer, Urushi in Japanese). To investigate the antitumor effect in vitro, a plant extract mixture was prepared from six medicinal herbs containing lacquer. The plant extract mixture containing lacquer (Rv-PEM) inhibited the proliferation of several mouse and human tumor cell lines. Rv-PEM had more potent inhibitory effect on the proliferation of human leukemia cell lines (MOLT-3, KG-1) than on other tumor cell lines. The IC50 values of Rv-PEM on MOLT-3 and KG-1 cells were 0.208 and 0.293 mg/mL, respectively. After treating Rv-PEM to the tumor cells, DNA fragmentation and Caspase-3 and -9 activity increased in the treated cells. The mechanisms of the inhibitory proliferation activity of Rv-PEM would involve apoptosis of human leukemia cells (MOLT-3, KG-1, K-562) by the mitochondrial pathway.
著者
石黒 武雄 古賀 直文 高村 恭治 丸山 哲生
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.75, no.7, pp.781-785, 1955-07-25 (Released:2010-02-19)
参考文献数
9
被引用文献数
8 8

The flowers of Osmanthus fragrans Lour. var. aurantiacus Makino were soaked in petroleum ether immediately after collection, digested for one week, and filtered with pressing. The aqueous layer of the filtrate was extracted with ether. The residual flowers were then digested with warm dehydrated ethanol for 16 hours.1) The portion soluble in petroleum ether is composed of concretes amounting to 0.214% of the original flowers and its treatment with cold dehydrated ethanol separates it into 0.163% of absolutes and 0.043% of flower wax, which is chiefly composed of triacontane, C30H62.2) The ether solution was chromatographically purified and p-hydroxyphenethyl alcohol C8H10O2, was isolated.3) The ethanol-soluble portion yielded D-mannitol.4) The water-soluble portion was fractionated with lead acetate and basic lead acetate. D-Mannitol was isolated from the filtrate and the presence of D-glucose and D-fructose was detected by paper chromatography. The precipitate obtained by lead acetate and the portion soluble in ethanol, yielded succinic acid.
著者
髙羽 里佳
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.58, no.10, pp.979, 2022 (Released:2022-10-01)
参考文献数
5

最近の報告から,マジックマッシュルームに含まれる幻覚成分であるシロシビンを治療抵抗性うつ病患者に投与したところ,2回の投与で,投与1週間後に患者の抑うつ症状が減少し,この作用は6か月間持続したことから,シロシビンが即効かつ持続的な抗うつ作用を有することが明らかとなった.その結果は,その後の臨床研究からも支持され,アメリカ食品医薬品局は,シロシビンがうつ病の画期的治療薬に成り得ると報告した.シロシビンをはじめとしたセロトニン作動性の幻覚薬が,うつ病のみならずアルコール依存症,不安障害,心的外傷後ストレス障害などに治療効果を示すとして,徐々に注目されはじめている.しかしながら,これらの薬物は,大脳皮質のセロトニン5-HT2A受容体(5-HT2AR)を刺激することにより,幻覚作用も誘発してしまうことがわかっている ため,治療薬としての応用には課題がある.本稿では,Gタンパク質共役型受容体の結晶構造を活用したリガンド探索により,マウスにおいて幻覚作用を示さずに,抗うつ様作用を示すリガンドの合成に成功したことを報告したCaoらの論文を紹介する.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) Carhart-Harris R. L. et al., Lancet Psychiatry, 3, 619-627(2016).2) U. S. FOOD & DRUG. Breakthrough therapy, 2019年1月4日.3) Michaiel A. M. et al., Cell Rep., 26, 3475-3483(2019).4) Cao D. et al., Science, 375, 403-411(2022).5) Thomas E. A. et al., Proc. Natl. Acad. Sci. U. S. A., 94, 14115-14119(1997).
著者
内山 奈穂子 宮澤 法政 河村 麻衣子 花尻(木倉) 瑠理 合田 幸広
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.2, pp.263-270, 2010-02-01 (Released:2010-02-01)
参考文献数
18
被引用文献数
14 16

Thirty-two psychotropic substances were listed as designated substances (Shitei-Yakubutsu, 31 compounds and 1 plant) in Japan by the Pharmaceutical Affairs Law in April 2007 for preventing the abuse of these substances. Subsequently, other psychoactive compounds were also added to this category, 40 substances (classified as 12 tryptamines, 17 phenethylamines, 3 piperazines, 6 alkyl nitrites, 1 diterpene and 1 plant) are controlled as designated substances as of July 2009. However, new designer drugs are still distributed in illegal drug market according to the results of our annual survey. This study presents the analysis of four newly distributed designer drugs detected from two products, which were purchased from October 2008 to February 2009 in Japan. As the results of NMR, GC-MS and LC-MS analyses, three phenethylamine derivertives, 1-(2-fluorophenyl)-N-methylpropan-2-amine (N-Me-2-FMP), 1-(2,5-dimethoxy-4-isopropylsulfanylphenyl)propan-2-amine (ALEPH-4) and 1-(2,5-dimethoxy-4-nitrophenyl)propan-2-amine (DON) and a tryptamine derivative, N-ethyl-5-methoxy-N-propyltryptamine (5-MeO-EPT), were detected. N-Me-2-FMP and 5-MeO-EPT were newly identified in this study. Additionally, ALEPH-4 and DON were found as novel illegal drugs distributed in Japan.
著者
水野 忠快
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.142, no.10, pp.1077-1082, 2022-10-01 (Released:2022-10-01)
参考文献数
12

As the term polypharmacology suggests, there are multiple actions of small-molecule compounds. We proposed a decomposition and understanding concept that sheds light on the small effects in comparison to the large effects by decomposing these multiple effects. This concept was embodied by describing the effects of the compounds in a transcriptome profile, followed by factor analysis to extract latent variables as decomposed effects. Application of this approach to public datasets resulted in the inferences of compound effects consistent with existing knowledge such as gene ontologies and pathways. In one experimental validation, the potential inducibility of endoplasmic reticulum stress of several commercial drugs was detected by decomposition. Another study successfully discriminated the effects of a natural product and its derivatives despite their structural similarity. In the era of big data, it is important to infer conceptual elements composed of measurable elements as a higher layer than the given data of a specimen, which can expand our perception and understanding of the specimen. This review introduces an example of such a philosophy by applying it to the multiple effects of drugs to contribute to the understanding.
著者
山崎 真巳
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.122, no.1, pp.47-56, 2002-01-01 (Released:2003-02-13)
参考文献数
36
被引用文献数
2 2

A molecular biological approach was applied to the study of diversity and regulation of secondary metabolism in medicinal plants at various levels. For the inter-species diversity, RFLP (restriction fragment length polymorphysm) and RAPD (random amplified polymorphic DNA) analyses of genomic DNA were performed on the plants, belonging to the same genus or family and containing related compounds. Phylogenetic trees of lupin alkaloid containing plants and other medicinal plants, based on RFLP and/or RAPD profiles, showed the relationship between the diversities in genomes and secondary metabolisms. The chemotypes regarding anthocyanin production in Perilla frutescens var. crispa, were subjected to the study on intra-species diversity. The structural genes and the regulatory genes involved in anthocyanin biosynthesis were isolated and their expression in red and green forms was determined by Northern blot analysis. The expression of all structural genes examined was co-ordinately regulated in form-specific manner and by light illumination. The anthocyanin production was enhanced in transgenic plants over-expressing Myc homologue genes from perilla. These results suggested that a protein complex including bHLH factors might regulate the expression of a series of structural genes. Additionally, cDNAs coding anthocyanin 5-O-glucosyltransferase and anthocyanidin synthase were isolated and characterized using recombinant proteins for the first time. In conclusion, it was indicated that the molecular biological techniques are powerful tools for the investigation of diversity and regulation of and for the genetic engineering of secondary metabolism in medicinal plants.
著者
本庄 美喜男
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.73, no.4, pp.368-371, 1953-04-25 (Released:2010-02-19)
参考文献数
21
被引用文献数
1 2

D-threo-β-Phenylserine was derived to 1-p-nitrophenyl-2-amino-1, 3-propanediol (I) which was found to be an optical antipode of (I) obtained by the hydrolysis of natural chloramphenicol. This confirms the fact that the steric configuration of natural chloramphenicol is the same as that of l-nor-φ-ephedrine.
著者
平野 光河 田頭 秀章 福永 浩司
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.134, no.6, pp.707-713, 2014 (Released:2014-06-01)
参考文献数
55
被引用文献数
7 10

We previously reported that the sigma-1 receptor is down-regulated in cardiomyocytes following heart failure in transverse aortic constriction (TAC) mice. In this review, we summarized the anti-hypertrophic action of selective sigma-1 receptor agonist, SA4503 in the hypertrophied cultured cardiomyocytes and discussed its possible mechanism of cardioprotection. Treatment with SA4503 (0.1-1 μM) dose-dependently inhibited hypertrophy in cultured cardiomyocytes induced by angiotensin II (Ang II). We also found that α1 receptor stimulation by phenylephrine (PE) promotes ATP production through IP3 receptor-mediated Ca2+ mobilization into mitochondria in cultured cardiomyocytes. Interestingly, the PE-induced ATP production was impaired after Ang II-induced hypertrophy and SA4503 treatment largely restored PE-induced ATP production. The impaired PE-induced ATP production was associated with reduced mitochondrial size. The SA4503 treatment completely restored mitochondrial size concomitant with restored ATP production. These effects were blocked by sigma-1 receptor antagonist, NE-100 and sigma-1 receptor siRNA. We also confirmed that chronic SA4503 administration also significantly attenuates myocardial hypertrophy and restores ATP production in transverse aortic constriction mice. Taken together, sigma-1 receptor stimulation with selective agonist SA4503 ameliorates cardiac hypertrophy and dysfunction by restoring both mitochondrial Ca2+ mobilization and ATP production via sigma-1 receptor stimulation. Sigma-1 receptor stimulation represents a new therapeutic strategy to rescue heart from hypertrophic dysfunction in heart failure.
著者
中村 庸輝
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.55, no.11, pp.1077, 2019 (Released:2019-11-01)
参考文献数
5

シグマ-1 受容体(Sig-1R)は,一回膜貫通型受容体であり,主に小胞体膜に発現しているタンパク質である.その細胞内での役割は,他のタンパク質の構造を安定化させるタンパク質(シャペロンタンパク質),またはイノシトール三リン酸(IP3)受容体などのタンパク質と物理的に会合し機能を調節する因子として働く.Sig-1Rは,慢性疼痛,筋萎縮性側索硬化症(ALS),精神疾患,認知機能障害など様々な末梢および中枢神経疾患の病態に深く関わっている可能性が報告されている一方で,その詳細には不明な点が多く残っている.内因性リガンドとしては,神経ステロイドであるプレグネノロン,プロゲステロンや,トリプトファンの代謝産物であるN, N-ジメチルトリプタミンが既に報告されているが,最近,Brailoiuらのグループによって新たなSig-1Rの内因性リガンドとしてコリンが同定されたので,本稿で紹介する.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) Schmidt H. R. et al., Nature, 532, 527-530(2016).2) Hayashi T., Su T. P., Cell, 131, 596-610(2007).3) Su T. P. et al., Science, 240, 219-221(1988).4) Fontanilla D. et al., Science, 323, 934-937(2009).5) Brailoiu E. et al., Cell Reports, 26, 330-337(2019).
著者
鴨志田 剛
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.57, no.11, pp.1052, 2021 (Released:2021-11-01)
参考文献数
4

生命とは何か? 生命の起源はどこか? 地球外に生命は存在するのか? これらの疑問は我々人類が長年持ち続け,未だ答えにたどり着けていない最大級の謎である.生命の起源に関しては,大きく分けて①神様が作ったという考え,②地球上で長い年月をかけて単純な物質が複雑に変化し誕生したという考え,③地球外からやってきたという考えの3つがある.①の考え方も素敵だが,科学的には②や③の説について深く議論されてきた.本稿では人類が生命の起源を探る際に考慮すべき点について最新の知見を基に述べたい.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) Kawaguchi Y. et al., Front. Microbiol., 11, 2050(2020).2) Cortesão M. et al., Front. Microbiol., 12, 601713(2021).3) Sielaff A. C. et al., Microbiome, 7, 50(2019).4) Bijlani S. et al., Front. Microbiol., 12, 639396(2021).