Discovery of innovative molecular targeted drugs based on Cancer Cell Informatics

2012 Fiscal Year Final Research Report

• Project/Area Number: 22240092
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Clinical oncology
• Research Institution: Japanese Foundation For Cancer Research
• Principal Investigator: YAMORI Takao 公益財団法人がん研究会, がん化学療法センター分子薬理部, 客員研究員 (60200854)
• Co-Investigator(Kenkyū-buntansha): DAN Shingo 公益財団法人がん研究会, がん化学療法センター・分子薬理部, 副部長 (70332202)
• Co-Investigator(Renkei-kenkyūsha): KAWADA Manabu 公益財団法人微生物化学研究会, 微生物化学研究センター・沼津創薬医科学研究所・創薬基盤研究ユニット, ユニット長 (20300808) ; NAKAMURA Hiroyuki 学習院大学, 理学部, 教授 (30274434) ; SHIINA Isamu 東京理科大学, 理学部, 教授 (40246690) ; KOJIMA Naoto 京都薬科大学, 創薬科学系・薬品製造学, 講師 (90420413) ; HIRONO Syuichi 北里大学, 薬学部, 教授 (30146328)
• Project Period (FY): 2010 – 2012
• Keywords: がん治療 / 分子標的薬 / 分子薬理学 / 情報システム

Research Abstract

We improved Cancer Cell Informatics that we originally developed to discover new anticancer drugs, and found a novel anticancer compound AMF-26. It destroyed Golgi apparatus, which controls membrane traffic, and inhibit the growth of cancer cells. AMF-26 induced complete regression of BSY-1 human breast cancer xenograft in nude mice by oral administration. Its toxicity was weak and recoverable. Therefore, AMF-26 is a promising novel anticancer drug candidate targeting Golgi apparatus

Research Products

• [Journal Article] Search for Novel Anti-tumor Agents from Ridaifens Using JFCR39, a Panel of Human Cancer Cell Lines (2013)
  • Author(s): Guo WZ, Wang Y, Umeda E, Shiina I, Dan S, Yamori T
  • Journal Title: Biol Pharm Bull Volume: 36(6) Pages: 1008-16
  • DOI: DOI:10.1248/bpb.b13-00129
  • Peer Reviewed
• [Journal Article] Cytotoxic Activity of Tivantinib (ARQ 197) Is Not Due Solely to c-MET Inhibition (2013)
  • Author(s): Katayama R, Aoyama A, Yamori T, Qi J, Oh-Hara T, Song Y, Engelman JA, Fujita N
  • Journal Title: Cancer Res Volume: 73(10) Pages: 3087-96
  • DOI: DOI:10.1158/0008-5472.CAN-12-3256
  • Peer Reviewed
• [Journal Article] Novel tamoxifen derivative Ridaifen-B induces Bcl-2 independent autophagy without estrogen receptor involvement (2013)
  • Author(s): Nagahara Y, Takeyoshi M, Sakemoto S, Shiina I, Nakata K, Fujimori K, Wang Y, Umeda E, Watanabe C, Uetake S, Yamori T, Dan S, Yoshimi Y, Shinomiya T, Ikekita M
  • Journal Title: Biochem Biophys Res Commun Volume: 435(4) Pages: 657-63
  • DOI: DOI:10.1016/j.bbrc.2013.05.040
  • Peer Reviewed
• [Journal Article] Total synthesis of AMF-26, an antitumor agent for inhibition of the Golgi system, targeting ADP-ribosylation factor 1 (2013)
  • Author(s): Shiina I, Umezaki Y, Ohashi Y, Yamazaki Y, Dan S, Yamori T
  • Journal Title: J Med Chem Volume: 56(1) Pages: 150-159
  • DOI: DOI:10.1021/jm301695c
  • Peer Reviewed
• [Journal Article] Identification of transporters associated with Etoposide sensitivity of stomach cancer cell lines and methotrexate sensitivity of breast cancer cell lines by quantitative targeted absolute proteomics (2013)
  • Author(s): Obuchi W, Ohtsuki S, Uchida Y, Ohmine K, Yamori T, Terasaki T
  • Journal Title: Mol Pharmacol Volume: 83(2) Pages: 490-500
  • DOI: DOI: 10.1124/mol.112.081083
  • Peer Reviewed
• [Journal Article] Synthesis of antitumor azolato-bridged dinuclear platinum(ii) complexes with in vivo antitumor efficacy and unique in vitro cytotoxicity profiles (2013)
  • Author(s): Komeda S, Takayama H, Suzuki T, Odani A, Yamori T, Chikuma M
  • Journal Title: Metallomics Volume: 5(5) Pages: 461-468
  • DOI: DOI:10.1039/c3mt00040k
  • Peer Reviewed
• [Journal Article] Structure-activity relationships of hybrid annonaceous acetogenins: Powerful growth inhibitory effects of their connecting groups between heterocycle and hydrophobic carbon chain bearing THF ring on human cancer cell lines (2013)
  • Author(s): Kojima N, Fushimi T, Tatsukawa T, Yoshimitsu T, Tanaka T, Yamori T, Dan S, Iwasaki H, Yamashita M
  • Journal Title: Eur J Med Chem Volume: 63C Pages: 833-839
  • DOI: DOI:10.1016/j.ejmech.2013.03.009
  • Peer Reviewed
• [Journal Article] Disruption of Tacc3 function leads to in vivo tumor regression (2013)
  • Author(s): Yao R, Natsume Y, Saiki Y, Shioya H, Takeuchi K, Yamori T, Toki H, Aoki I, Saga T, Noda T
  • Journal Title: Oncogene Volume: 31(2) Pages: 135-148
  • DOI: DOI:10.1038/onc.2011.235
  • Peer Reviewed
• [Journal Article] AMF-26, a Novel Inhibitor of the Golgi System, Targeting ADP-ribosylation Factor 1 (Arf1) with Potential for Cancer Therapy (2012)
  • Author(s): Ohashi Y, Iijima H, Yamaotsu N, Yamazaki K, Sato S, Okamura M, Sugimoto K, Dan S, Hirono S, Yamori T
  • Journal Title: J Biol Chem Volume: 287(6) Pages: 3885-3897
  • DOI: DOI:10.1074/jbc.M111.316125
  • Peer Reviewed
• [Journal Article] Isolation and structures of biselyngbyasides B, C, and D from the marine cyanobacterium Lyngbya sp., and the biological activities of biselyngbyasides (2012)
  • Author(s): Morita M, Ohno O, Teruya T, Yamori T, Inuzuka T, Suenaga K
  • Journal Title: Tetrahedron Volume: 68(29) Pages: 5984-5990
  • DOI: DOI:10.1016/j.tet.2012.05.038
  • Peer Reviewed
• [Journal Article] JFCR39, a panel of 39 human cancer cell lines, and its application in the discovery and development of anticancer drugs (2012)
  • Author(s): Kong D, Yamori T
  • Journal Title: Bioorg Med Chem Volume: 20(6) Pages: 1947-1951
  • DOI: DOI:10.1016/j.bmc.2012.01.017
  • Peer Reviewed
• [Journal Article] Cleavage mechanism and anti-tumor activity of 3,6-epidioxy-1,10-bisaboladiene isolated from edible wild plants (2012)
  • Author(s): Kimura KI, Sakamoto Y, Fujisawa N, Uesugi S, Aburai N, Kawada M, Ohba SI, Yamori T, Tsuchiya E, Koshino H
  • Journal Title: Bioorg Med Chem Volume: 20(12) Pages: 3887-3897
  • DOI: DOI:10.1016/j.bmc.2012.04.025
  • Peer Reviewed
• [Journal Article] Development of an immunohistochemical protein quantification system in conjunction with tissue microarray technology for identifying predictive biomarkers for phosphatidylinositol 3-kinase inhibitors (2012)
  • Author(s): Isoyama S, Yoshimi H, Dan S, Okamura M, Seki M, Irimura T, Yamori T
  • Journal Title: Biol Pharm Bull Volume: 35(9) Pages: 1607-1613
  • DOI: DOI:10.1248/bpb.b12-00327
  • Peer Reviewed
• [Journal Article] Establishment of phosphatidylinositol 3-kinase inhibitor-resistant cancer cell lines and therapeutic strategies for overcoming the resistance (2012)
  • Author(s): Isoyama S, Dan S, Nishimura Y, Nakamura N, Kajiwara G, Seki M, Irimura T, Yamori T
  • Journal Title: Cancer Sci Volume: 103(11) Pages: 1955-1960
  • DOI: DOI:10.1111/cas.12004
  • Peer Reviewed
• [Journal Article] ZSTK474, a specific phosphatidylinositol 3-kinase inhibitor, induces G1 arrest of the cell cycle in vivo (2012)
  • Author(s): Dan S, Okamura M, Mukai Y, Yoshimi H, Inoue Y, Hanyu A, Sakaue-Sawano A, Imamura T, Miyawaki A, Yamori T
  • Journal Title: Eur J Cancer Volume: 48(6) Pages: 936-943
  • DOI: DOI:10.1016/j.ejca.2011.10.006
  • Peer Reviewed
• [Journal Article] Improving drug potency and efficacy by nanocarrier-mediated subcellular targeting (2011)
  • Author(s): Murakami M, Cabral H, Matsumoto Y, Wu S, Kano MR, Yamori T, Nishiyama N, Kataoka K
  • Journal Title: Sci Transl Med Volume: 3(64) Pages: 64-62
  • DOI: DOI:10.1126/scitranslmed.3001385
  • Peer Reviewed
• [Journal Article] Design and synthesis of C35-fluorinated solamins and their growth inhibitory activities against human cancer cell lines (2011)
  • Author(s): Kojima N, Suga Y, Hayashi H, Yamori T, Yoshimitsu T, Tanaka T
  • Journal Title: Bioorg Med Chem Lett Volume: 21(19) Pages: 5745-5749
  • DOI: DOI:10.1016/j.bmcl.2011.08.011
  • Peer Reviewed
• [Journal Article] Total synthesis and biological assessment of (-)-exiguolide and analogues (2011)
  • Author(s): Fuwa H, Suzuki T, Kubo H, Yamori T, Sasaki M
  • Journal Title: Chemistry Volume: 17(9) Pages: 2678-2688
  • DOI: DOI: 10.1002/chem.201003135
  • Peer Reviewed
• [Journal Article] Effectiveness of combined treatment using X-rays and a phosphoinositide 3-kinase inhibitor, ZSTK474, on proliferation of HeLa cells in vitro and in vivo (2011)
  • Author(s): Anzai K, Sekine-Suzuki E, Ueno M, Okamura M, Yoshimi H, Dan S, Yaguchi S, Enami J, Yamori T, Okayasu R
  • Journal Title: Cancer Sci Volume: 102(6) Pages: 1176-1180
  • DOI: DOI:10.1111/j.1349-7006
  • Peer Reviewed
• [Journal Article] Cytochrome P450 1B1 gene polymorphisms as predictors of anticancer drug activity: studies with in vitro models (2010)
  • Author(s): Laroche-Clary A, Le Morvan V, Yamori T, Robert J
  • Journal Title: Mol Cancer Ther Volume: 9(12) Pages: 3315-3321
  • DOI: DOI:10.1158/1535-7163.MCT-10-0673
  • Peer Reviewed
• [Journal Article] ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor identified using the JFCR39 drug discovery system (2010)
  • Author(s): Kong DX, Yamori T
  • Journal Title: Acta Pharmacol Sin Volume: 31(9) Pages: 1189-1197
  • DOI: DOI: 10.1038/aps.2010.150
  • Peer Reviewed
• [Journal Article] Discovery of phosphatidylinositol 3-kinase inhibitory compounds from the Screening Committee of Anticancer Drugs (SCADS) library (2010)
  • Author(s): Kong D, Yamazaki K, Yamori T
  • Journal Title: Biol Pharm Bull Volume: 33(9) Pages: 1600-1604
  • URL: https://www.jstage.jst.go.jp/article/bpb/33/9/33_9_1600/_article
  • Peer Reviewed
• [Journal Article] Inhibition profiles of phosphatidylinositol 3-kinase inhibitors against PI3K superfamily and human cancer cell line panel JFCR39 (2010)
  • Author(s): Kong D, Dan S, Yamazaki K, Yamori T
  • Journal Title: Eur J Cancer Volume: 46(6) Pages: 1111-1121
  • DOI: DOI:10.1016/j.ejca.2010.01.005
  • Peer Reviewed
• [Journal Article] Convergent synthesis of fluorescence-labeled probes of Annonaceous acetogenins and visualization of their cell distribution (2010)
  • Author(s): Kojima N, Morioka T, Urabe D, Yano M, Suga Y, Maezaki N, Ohashi-Kobayashi A, Fujimoto Y, Maeda M, Yamori T, Yoshimitsu T, Tanaka T
  • Journal Title: Bioorg Med Chem Volume: 18(24) Pages: 8630-8641
  • DOI: DOI:10.1016/j.bmc.2010.10.004
  • Peer Reviewed
• [Journal Article] Ishikawa Y, Yamori T. Correlating phosphatidylinositol 3-kinase inhibitor efficacy with signaling pathway status: in silico and biological evaluations (2010)
  • Author(s): Dan S, Okamura M, Seki M, Yamazaki K, Sugita H, Okui M, Mukai Y, Nishimura H, Asaka R, Nomura K, Ishikawa Y, Yamori T
  • Journal Title: Cancer Res Volume: 70(12) Pages: 4982-4994
  • DOI: DOI:10.1158/0008-5472.CAN-09-4172
  • Peer Reviewed
• [Journal Article] Synthesis and preclinical evaluations of 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one monosodium phosphate (CHM-1-P-Na) as a potent antitumor agent (2010)
  • Author(s): Chou LC, Chen CT, Lee JC, Way TD, Huang CH, Huang SM, Teng CM, Yamori T, Wu TS, Sun CM, Chien DS, Qian K,Morris-Natschke SL, Lee KH, Huang LJ, Kuo SC
  • Journal Title: J Med Chem Volume: 53(4) Pages: 1616-1626
  • DOI: DOI:10.1021/jm901292j.
  • Peer Reviewed
• [Presentation] Identification of a new inhibitor of the Golgi system, targeting ADP-ribosylation Factor 1 (Arf1) with potential for cancer therapy (2012)
  • Author(s): Ohashi Y, Iijima H, Yamaotsu N, Yamazaki K, Sato S, Okamura M, Sugimoto K, Dan S, Hirono S, Yamori T
  • Organizer: 2012AACR Annual Meeting
  • Place of Presentation: Chicago, USA
  • Year and Date: 20120331-0404
• [Presentation] Discovery of Molecular-Targeted Drugs by an information-rich Cancer Cell Line Panel (2012)
  • Author(s): Yamori T
  • Organizer: "JFCR39 ". 理研・マックスプランク研究所合同シンポジウム
  • Place of Presentation: ドイツ
  • Year and Date: 20120305-07
• [Presentation] Identification of a Novel Pi3k Inhibitor for Cancer Treatment (2010)
  • Author(s): Yamori T
  • Organizer: 世界薬学会議 2010 FIP PSWC/AAPS Annual Meeting
  • Place of Presentation: New Orleans, USA
  • Year and Date: 20101114-18
• [Book] JFCR39がん細胞パネルの活用による新たな抗がん剤創薬 (2012)
  • Author(s): 矢守隆夫, 大橋愛美
  • Publisher: 実験医学
• [Remarks]
  • URL: http://www.jfcr.or.jp/laboratory/researcher/2387.html
• [Patent(Industrial Property Rights)] 『新規化合物及びその製造方法並びに抗がん剤』 (2012)
  • Inventor(s): (がん研)矢守隆夫、(東京理科大)椎名勇、中田健也、(東京電機大)長原礼宗
  • Industrial Property Rights Holder: 学校法人 東京理科大学、 学校法人 東京電機大学、 公益財団法人がん研究会
  • Industrial Property Number: 特願2012-104763
  • Filing Date: 2012-05-06
• [Patent(Industrial Property Rights)] 『新規化合物及びその製造方法並びに抗がん剤』 (2012)
  • Inventor(s): (がん研究会)矢守隆夫、(東京理科大)椎名勇
  • Industrial Property Rights Holder: 学校法人東京理科大学、公益財団法人がん研究会
  • Industrial Property Number: 特願2012-087973
  • Filing Date: 2012-04-06