Search Results 1-20 of 98

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  • Drug resistance in cancer therapy and the possible role of epigenetics

    Asano Takeshi

    … With conventional anti-cancer drugs, including alkylating drugs, anti-metabolite drugs, topoisomerase inhibitors, and microtubule inhibitors, which have been available for half a century, the drug resistance often occurs due to decreased expression of target enzymes, with increased expression of drug export pumps. …

    Journal of Nippon Medical School, 2020


  • Middle Molecular and Conjugation Strategies for Development of Bioactive Middle Molecules  [in Japanese]

    Manabe Yoshiyuki , Shimoyama Atushi , Kabayama Kazuya , Fukase Koichi

    … These conjugated compounds are called small molecule drug conjugates (SMDC), which are a class of medium-sized drugs. …

    Journal of Synthetic Organic Chemistry, Japan 78(5), 527-537, 2020


  • Discovery of Molecular Glues to Induce Selective Protein Degradation, Leading to Development of New Modalities with Targeted Protein Knockdown Function  [in Japanese]

    Uehara Taisuke , Owa Takashi

    … Importantly, the molecular glue story has recently been extended to synthetic small molecule space as well. … Clinically important myeloma drug lenalidomide and other immunomodulatory imide drugs (IMiDs) were found to hijack the cullin 4 (CUL4)-RING E3 ubiquitin ligase system by binding to the one of DDB1- and CUL4-associated proteins (DCAFs), cereblon (CRBN), to redirect the substrate selectivity of CRBN. …

    Journal of Synthetic Organic Chemistry, Japan 78(5), 414-420, 2020


  • Design and Synthesis of 2-(1-Alkylaminoalkyl)pyrazolo[1,5-a]pyrimidines as New Respiratory Syncytial Virus Fusion Protein Inhibitors

    Yamaguchi-Sasaki Toru , Ueda-Yonemoto Naoko , Tanigawa Eiji , Abe-Kumasaka Tomoko , Sugiyama Hiroyuki , Kanuma Kosuke , Tamura Yunoshin , Ogata Yuya , Kawaguchi Takanori , Kurosaka Jun , Sugaya Yutaka , Iwakiri Kanako , Busujima Tsuyoshi , Takahashi Ryo

    … Although two drugs have been approved for the treatment of RSV infections, the low therapeutic index of these drugs have led pharmaceutical companies to develop safe and effective small-molecule anti-RSV drugs. …

    Chemical and Pharmaceutical Bulletin 68(4), 345-362, 2020


  • Semi-rational Design of Target-binding Small Proteins for Cancer Treatment  [in Japanese]

    Kadonosono Tetsuya , Kizaka-Kondoh Shinae

    … <p>Small proteins that have a high affinity for cancer cell surface markers can be promising cheap alternatives to antibodies (antibody mimetics). … We recently found that a target-binding peptide binds to its target molecule more strongly when it is structurally constrained. … To apply this finding to the development of chemically synthesizable small antibody mimetics, we have established an efficient method of creating such proteins, named fluctuation-regulated affinity proteins (FLAPs). …

    YAKUGAKU ZASSHI 140(2), 159-162, 2020


  • Investigation of Drug-induced Lung Injury for the Development of a Novel Therapeutic Approach  [in Japanese]

    Kawami Masashi

    … <p>The development of serious lung diseases, such as pulmonary fibrosis, is associated with several drugs. … In addition, our results showed that certain secreted factors and microRNAs, a class of small noncoding RNAs, may be involved in MTX-induced EMT. … The effects of COA-Cl, a novel synthetic small molecule, on TGF-β1-induced EMT were evaluated to determine the therapeutic potential of COA-Cl against drug-induced lung injury. …

    YAKUGAKU ZASSHI 140(1), 15-22, 2020

    J-STAGE  Ichushi Web 

  • Re-energizing Small Molecule Drug Discovery with Centaur Chemist  [in Japanese]

    田中 大輔

    薬学図書館 = Pharmaceutical library bulletin 64(4), 193-199, 2019

    Ichushi Web 

  • Drug development of fibrodysplasia ossificans progressiva (FOP) focused on constitutive activation of FOP-ACVR1  [in Japanese]

    Zhao Chengzhu , Ohta Akira , Ikeya Makoto , Hino Kyosuke , Horigome Kazuhiko , Nishio Megumi , Okanishi Yasue , Nagata Sanae , Komura Shingo , Yamada Yasuhiro , Toguchida Junya

    … Despite numerous studies, no drugs have been approved for FOP. … After HTS 5,000 small molecule compounds, we identified two hit compounds that are effective at suppressing the enhanced chondrogenesis of FOP patient-derived iPSCs (FOP-iPSCs) and suppressed the HO of multiple model mice, including FOP-ACVR1 transgenic mice and HO model mice utilizing FOP-iPSCs. …

    Proceedings for Annual Meeting of The Japanese Pharmacological Society 92(0), 1-YIA-32, 2019


  • Conformation control of molecules at interfaces  [in Japanese]

    Nakanishi Waka

    <p>各々のコンフォメーションは1-数kcal/molの比較的小さいエネルギー差をもって制御されるが,これは巨大分子であるタンパク質の高効率な機能発現にとって重要である.一方,薬などの小分子では,これまでは,コンフォメーションをむしろ固定する手法が多くとられてきた.小さなエネルギー制御を必要とするコンフォメーション制御は小分子では簡単ではないが,低次元場である界面を用いることで可能とな …

    Abstract book of Annual Meeting of the Japan Society of Vacuum and Surface Science 2019(0), 2Fp09, 2019


  • Pharmacology and safety profiles prediction platform: Chemotargets CLARITY  [in Japanese]

    MIDORIKAWA Atsushi , KIMURA Toshiro , MESTRES Jordi

    … <p>Chemotargets CLARITY is an integrative analytics platform that assembles pharmacology and safety intelligence of drugs and allows for predicting the pharmacology and safety profiles of novel small molecule pharmaceuticals and cosmeceuticals. …

    Annual Meeting of the Japanese Society of Toxicology 46.1(0), P-185, 2019


  • Structural Basis of the Multifunctional Hub Protein and Identification of a Small-molecule Compound for Drug Discovery  [in Japanese]

    Hara Kodai

    … Thus, TLS enables cancer cells to acquire resistance to alkylate anticancer drugs. … Furthermore, we found a small-molecule compound that inhibits TLS by targeting the REV7-REV3 PPIs. … These findings improve our understanding of multifunctional hub proteins, and are helpful for designing small-molecule compounds for novel anticancer drug development.</p> …

    YAKUGAKU ZASSHI 139(7), 969-973, 2019

    J-STAGE  Ichushi Web 

  • Molecular Pharmacological Approaches for Treating Abdominal Aortic Aneurysm

    Miyake Takashi , Miyake Tetsuo , Kurashiki Tomohiro , Morishita Ryuichi

    … Although many patients with a small AAA are detected during routine abdominal screening, there is no effective therapeutic option to prevent the progression or regression of AAA in the clinical setting. … Regulation of these factors using nucleic acid drugs is expected to be a novel therapeutic option for AAA. …

    Annals of Vascular Diseases 12(2), 137-146, 2019

    J-STAGE  Ichushi Web 

  • An mTOR Signaling Modulator Suppressed Heterotopic Ossification ofFibrodysplasia Ossificans Progressiva

    Hino Kyosuke , Zhao Chengzhu , Horigome Kazuhiko , Nishio Megumi , Okanishi Yasue , Nagata Sanae , Komura Shingo , Yamada Yasuhiro , Toguchida Junya , Ohta Akira , Ikeya Makoto

    FOPにおける骨化を抑える新たな候補物質の同定 --治療法探索へ新しい戦略への可能性を拓く--. 京都大学プレスリリース. 2018-11-02.

    Stem Cell Reports 11(5), 1106-1119, 2018-11-13


  • Resistance to Anti-Angiogenic Therapy in Cancer—Alterations to Anti-VEGF Pathway

    Itatani Yoshiro , Kawada Kenji , Yamamoto Takamasa , Sakai Yoshiharu

    … In addition, the other VEGF pathway inhibitors including small molecule tyrosine kinase inhibitors (sunitinib, sorafenib, and pazopanib), a soluble VEGF decoy receptor (aflibercept), and a humanized monoclonal antibody of VEGF receptor 2 (VEGFR2) (ramucirumab) have been approved for cancer therapy. … The primary or acquired resistance towards many oncological drugs, including anti-VEGF inhibitors, is a common problem in cancer treatment. …

    International Journal of Molecular Sciences 19(4), 2018-04-18


  • Changing Paradigm of Pharmaceutical Manufacturing  [in Japanese]

    タキザワ バヤン , ボーン ステファン , シェン エリン , テスタ クリストファー , フ チャントン , マーシャ サルバトーレ , 池應 真実 [訳] , 原田 恒樹 [訳]

    製剤機械技術学会誌 = Journal of pharmaceutical machinery and engineering 27(1), 15-22, 2018

  • From the small molecule drug discovery engine to the next generation drug discovery platform, challenge in Shionogi & Co., Ltd.  [in Japanese]

    Shiota Takeshi

    <p>我々塩野義製薬は「創薬型製薬企業として社会とともに成長する」をビジョンに中期経営計画Shionogi Growth Strategy 2020(SGS2020)を宣言し、世界の患者さんに最も必要とされる新薬の創製に取り組んでいる。継続的な新薬創製にはそれを可能とするプラットフォームと呼べる研究アセットが必要であり、そのような強みを構築できるか否かが競争力の源泉となる。我々は低分子 …

    MEDCHEM NEWS 28(4), 154-159, 2018


  • Innovative growth of biopharmaceuticals  [in Japanese]

    Tsuchiya Masayuki

    <p> 1953年にDNA二重らせん構造が提唱され,塩基配列が遺伝情報を担っていることが説明された.その後,分子生物学は目覚しい発展を遂げ,遺伝子組み換え技術などバイオテクノロジーによって画期的なバイオ医薬品が次々に誕生した.2017年の日本のバイオ医薬品の市場は1兆4千億円に達し,そしてその61%は抗体医薬品である.今後もバイオ医薬品は通常の医薬品の倍近い市場成長率を示すことが予想さ …

    Clinical Rheumatology and Related Research 30(4), 255-261, 2018

    J-STAGE  Ichushi Web 

  • Oral drug delivery system targeting intestinal transporters  [in Japanese]

    Fujita Daichi , Tamai Ikumi

    <p>薬物の消化管吸収は体内動態を左右する重要な因子であり、医薬品の経口製剤化が求められる中で吸収性の改善を目的として経口DDSの開発が進められている。トランスポーターは、化合物の消化管吸収・組織移行性に関わることから、薬物の膜透過性向上の標的として期待される。また最近では、トランスポーターが膜表面タンパク質であることから、基質認識性を利用したDDSキャリアの表面修飾によってトランスポ …

    Drug Delivery System 33(5), 377-389, 2018

    J-STAGE  Ichushi Web 

  • Development of an <i>In Vitro</i> System for Evaluating Intestinal Drug Disposition Using Human Induced Pluripotent Stem Cell-Derived Intestinal Epithelial Cells  [in Japanese]

    Iwao Takahiro

    … Tissues of the small intestine are crucial to understanding drug disposition because these tissues regulate the bioavailability of drugs. … An improved intestinal differentiation method was established by screening a variety of small molecule compounds against cells during differentiation. …

    YAKUGAKU ZASSHI 138(10), 1241-1247, 2018

    J-STAGE  Ichushi Web 

  • Analysis of Time-to-Onsets of Drug-Induced Blood Disorders with Small Molecule Molecularly-Targeted Drugs

    Komada Fusao

    … of small molecule molecularly-targeted drugs via the use of the spontaneous adverse reaction reporting system of the Japanese Adverse Drug Event Report (JADER) database.<br><b>Methods: </b>The JADER database from April 2004 to March 2017 was downloaded from the Pharmaceuticals and Medical Devices Agency (PMDA) website.  The DIBD dataset for small molecule molecularly-targeted drugs was …

    Iyakuhin Johogaku 20(1), 29-35, 2018

    J-STAGE  Ichushi Web 

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