★主要研究テーマ:
免疫チェックポイント阻害剤のインシリコ創薬(静岡県立静岡がんセンター研究所 免疫治療研究部静岡県環境衛生科学研究所 医薬食品部 医薬班との共同研究)
・生体高分子-低分子複合体の分子モデリングによる相互作用解析とヴァーチャルスクリーニング

  • ◎山口 健、楠原 正俊、芹澤 昌邦、望月 徹、大島 啓一、畠山 慶一、浦上 研一、大浪 俊平、秋山 靖人、丸山 宏ニ、井上 謙吾、下田 勇治、長嶋 剛史、石川 吉伸 がんの発症リスクの有無を判定する方法 WO/2018/025971(平成30年2月8日公開)(静岡県立静岡がんセンター研究所との共同研究)

ハロゲン結合やハロゲン···ハロゲン相互作用を示すクロモンキノロンキナゾリノン類の合成とX線結晶構造解析
・金属酵素(インフルエンザウィルスRNAポリメラーゼPANウレアーゼメタロ-β-ラクタマーゼ)の阻害剤の創製
・計算化学的手法による天然物や合成化合物の立体配座解析とCDスペクトルやNMR化学シフトの予測
・tRNAエピトランスクリプトーム創薬で実現するがん幹細胞標的型抗がん剤のインシリコ創薬(岡山大学 大学院医歯薬学総合研究科(細胞生理/生理学I) 藤村 篤史先生との共同研究)
ポリ(ADP-リボース)分解酵素(PARG)阻害剤のインシリコ創薬長崎大学大学院医歯薬学総合研究科 益谷 美都子 先生との共同研究)

  • ◎益谷 美都子、佐久間 浩彰、佐々木 由香、小泉 史明、下山 達、井上 謙吾、松野 研司、大川原 正、イスラム ラフィクル、高村 岳樹、入江 徹美、石川 吉伸(特許出願)新規抗がん薬 特願2015-211575(平成27年10月28日出願)
  • ◎益谷 美都子、佐久間 浩彰、佐々木 由香、小泉 史明、小寺 康夫、佐々木 貴之、下山 達、井上 謙吾、松野 研司、大川原 正、イスラム ラフィクル、高村 岳樹、入江 徹美、石川 吉伸 新規抗がん薬 WO2017073065(平成29年5月4日公開)

Cdkal1リスクアレル保有2型糖尿病患者に対する治療薬のインシリコ創薬(熊本大学大学院生命科学研究部分子生理学 富澤一仁 先生との共同研究)

インシリコ創薬・分子モデリングに関する紹介はコチラを御覧ください。

★2001年以降の学術論文(リンクが張ってあります):

82)Odonbayar B, Murata T, Suganuma K, Ishikawa Y, Buyankhishig B, Batkhuu J, Sasaki K.
Acylated Lignans Isolated from Brachanthemum gobicum and Their Trypanocidal Activity

J. Nat. Prod., in press.


81) Miyata R, Sahlan M, Ishikawa Y, Hashimoto H, Honda S, Kumazawa S.
Propolis components from stingless bees collected on South Sulawesi, Indonesia, and their xanthine oxidase inhibitory activity

J. Nat. Prod., 82, 205-210 (2019).


80) Nagasaka Y, Asakawa T, Shintaku S, Masuda A, Matsumura K, Inai M, Ishikawa Y, Egi M, Hamashima Y, Kan T.
Concise Synthesis of TAN1251C

Heterocycles, in press.

79) Derayea SM, Tsujino H, Oyama Y,Ishikawa Y, Yamashita T, Uno T.
Investigation on drug-binding in heme pocket of CYP2C19 with UV-visible and resonance Raman spectroscopies

Spectrochim. Acta A, 209, 209-216 (2019).

78)Yokoyama H, Sawada J, Sato K, Ogo N, Kamei N, Ishikawa Y, Hara K, Asai A, Hashimoto H.
Structural and Thermodynamic Basis of the Enhanced Interaction between Kinesin Spindle Protein Eg5 and STLC-type Inhibitors

ACS Omega, 3, 12284-12294 (2018).


77)Hara K, Uchida M, Tagata R, Yokoyama H, Ishikawa Y, Hishiki H, Hashimoto H.
Structure of PCNA bound to APIM peptide reveals universality of PCNA interaction

Acta Cryst. F74, 214-221 (2018).


76) Hara K, Taharazako S, Ikeda M, Fujita H, Mikami Y, Kikuchi S, Hishiki A, Yokoyama H, Ishikawa Y, Kanno S, Tanaka K, Hashimoto H.
Dynamic feature of mitotic arrest deficient 2-like protein 2 (MAD2L2) and structural basis for its interaction with chromosome alignment maintaining phosphoprotein (CAMP)

J. Biol. Chem. 292, 17658-17667 (2017).

75) Konishi H, Matsubara M, Mori K, Tokiwa T, Arulmozhiraja S, Yamamoto Y, Ishikawa Y, Hashimoto H, Shigeta Y, Tokiwa H, Manabe K.
Mechanistic Insight into Weak-Base-Catalyzed Generation of Carbon Monoxide from Phenyl Formate and Its Application to Catalytic Carbonylation at Room Temperature without Use of External Carbon Monoxide Gas

Adv. Synth. Catal., 359, 3592-3601 (2017).

74) Nagasaka Y, Shintaku S, Matsumura K, Masuda A, Asakawa T, Inai M, Egi M, Hamashima Y, Ishikawa Y, Kan T.
Total Synthesis of TAN1251C via Diastereoselective Construction of the Azaspiro Skeleton

Org. Lett., 19, 3839-3842 (2017).


73) Ishikawa Y.
Crystal structure of 7-iodo-4-oxo-4H-chromene-3-carbaldehyde

Acta Cryst. E72, 1724-1727 (2016).

72) Murata T, Ishikawa Y, Saruul E, Selenge E, Sasaki K, Umehara K, Yoshizaki F, Batkhuu J.
Abietane-type diterpenoids from the roots of Caryopteris mongolica and their cholinesterase inhibitory activities

Phytochemistry, 130, 152-158 (2016).

71) Ishikawa Y.
Crystal structure of 6,7-di­chloro-4-oxo-4H-chromene-3-carbaldehyde

Acta Cryst. E71, o652-o653 (2015).

70) Ogo N, Ishikawa Y, Sawada J, Matsuno K, Hashimoto A, Asai A.
Structure-guided Design of Novel L-Cysteine Derivatives as Potent KSP Inhibitors

ACS Med. Chem. Lett., 6, 1004-1009 (2015).

69) Ishikawa Y.
Crystal structure of 4-oxo-4H-chromene-3-carb­oxy­lic acid

Acta Cryst. E71, o580-o581 (2015).

68) Ishikawa Y.
Crystal structure of 8-bromo-4-oxo-4H-chromene-3-carbaldehyde

Acta Cryst. E71, o572-o573 (2015).

67) Ishikawa Y, Yoshida N.
Crystal structure of ethyl 8-chloro-4-oxo-1,4-di­hydro­quinoline-3-carboxyl­ate

Acta Cryst. E71, o566 (2015).

66) Ishikawa Y.
Crystal structure of 7,8-di­chloro-4-oxo-4H-chromene-3-carbaldehyde

Acta Cryst. E71, 902-905 (2015).

65) Ishikawa Y.
Crystal structure of 3-acetyl-4H-chromen-4-one

Acta Cryst. E71, o527 (2015).

64) Ishikawa Y.
Crystal structure of 6-bromo-7-fluoro-4-oxo-4H-chromene-3-carbaldehyde

Acta Cryst. E71, 857-860 (2015).

63) Ishikawa Y.
Crystal structure of 3-(hy­droxy­meth­yl)chromone

Acta Cryst. E71, o495 (2015).

62) Yokoyama H, Sawada J, Katoh S, Matsuno K, Ogo N, Ishikawa Y, Hashimoto H, Fujii S, Asai A.
Structural Basis of New Allosteric Inhibition in Kinesin Spindle Protein Eg5

ACS Chem. Biol., 10, 1128-1136 (2015).


61) Ishikawa Y, Motohashi Y.
Crystal structure of (3,5-dichloro-2-hydroxyphenyl){1-[(naphthalen-1-yl)carbonyl]-1H-pyrazol-4-yl}methanone

Acta Cryst. E70, 522-524 (2014).

60) Ishikawa Y, Motohashi Y.
Crystal structure of (3,5-dibromo-2-hydroxyphenyl){1-[(naphthalen-1-yl)carbonyl]-1H-pyrazol-4-yl}methanone


Acta Cryst. E70, o1033 (2014).

59) Ishikawa Y.
Crystal structure of 7-bromo-4-oxo-4H-chromene-3-carbaldehyde

Acta Cryst. E70, o996 (2014).


58) Todoroki K, Nakano T, Watanabe H, Min JZ, Inoue K, Ishikawa Y, Toyo’oka T.
Computational Prediction of Diastereomeric Separation Behavior of Fluorescent o-Phthalaldehyde Derivatives of Amino Acids.

Anal. Sci., 30, 865-870 (2014).

57) Ishikawa Y.
7-Chloro-4-oxo-4H-chromene-3-carbaldehyde

Acta Cryst., E70, o831 (2014).

56) Ishikawa Y, Watanabe K.
(E)-3,4,5-trimethoxy-N'-((6-methoxy-4-oxo-4H-chromen-3-yl)methylene)benzohydrazide monohydrate

Acta Cryst., E70, o832 (2014)

55) Ishikawa Y.
6-Chloro-7-fluoro-4-oxo-4H-chromene-3-carbaldehyde

Acta Cryst., E70, o825 (2014).

54) Ishikawa Y.
6-Chloro-7-methyl-4-oxo-4H-chromene-3-carbaldehyde

Acta Cryst., E70, o804 (2014).

53) Ishikawa Y, Watanabe K.
(E)-4-Methoxy-N'-[(6-methyl-4-oxo-4H-chromen-3-yl)methylidene]benzohydrazide monohydrate

Acta Cryst., E70, o784 (2014).

52) Ishikawa Y.
8-Fluoro-4-oxo-4H-chromene-3-carbaldehyde

Acta Cryst., E70, o774 (2014).

51) Ishikawa Y.
6-Iodo-4-oxo-4H-chromene-3-carbaldehyde

Acta Cryst., E70, o744 (2014).

50) Ishikawa Y.
8-Chloro-4-oxo-4H-chromene-3-carbaldehyde

Acta Cryst., E70, o743 (2014).

49) Ishikawa Y, Yoshida N.
Ethyl 8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate

Acta Cryst., E70, o719 (2014).

48) Ishikawa Y. Sugisawa Y.
Diethyl 7,7'-4-oxo-4H-[1,4'-biquinoline]-3,3'-dicarboxylate

Acta Cryst., E70, o655 (2014).

47) Ishikawa, Y.
6-Fluoro-4-oxo-4H-chromene-3-carbaldehyde

Acta Cryst., E70, o583 (2014).

46) Ishikawa Y, Watanabe K.
(E)-4-Methyl-N’-[(4-oxo-4H-chromen-3-yl)methylene]benzohydrazide

Acta Cryst., E70, o565 (2014).

45) Ishikawa Y.
6-Bromo-4-oxo-4H-chromene-3-carbaldehyde

Acta Cryst., E70, o555 (2014).

44) Ishikawa Y.
6-Chloro-8-nitro-4-oxo-4H-chromene-3-carbaldehyde

Acta Cryst., E70, o547 (2014).

43) Ishikawa Y.
6,8-Diiodo-4-oxo-4H-chromene-3-carbaldehyde

Acta Cryst., E70, o536 (2014).

42) Ishikawa Y, Yoshida N.
Diethyl 4-oxo-4H-[1,4'-biquinoline]-3,3'-dicarboxylate

Acta Cryst., E70, o523 (2014).

41) Ishikawa Y.
6-Chloro-4-oxo-4H-chromene-3-carbaldehyde

Acta Cryst., E70, o514 (2014).

40) Ishikawa Y, Watanabe K.
(E)-3,4,5-Trimethoxy-N’-[(4-oxo-4H-chromen-3-yl)methylidene]benzohydrazide

Acta Cryst., E70, o472 (2014).

39) Ishikawa Y, Suzuki T, Yoshida N.
3-Acetyl-2-fluoro-6H-benzo[c]chromen-6-one


Acta Cryst., E70, o470-o471 (2014).

38) Ishikawa Y.
6,8-Dibromo-4-oxo-4H-chromene-3-carbaldehyde

Acta Cryst., E70, o439 (2014).

37) Ishikawa Y.
A Script for Automated 3-Dimentional Structure Generation and Conformer Search from 2-Dimentional Chemical Drawing

Bioinformation, 9, 988-992 (2013).

36) Ishikawa Y, Yoshida N, Suzuki T.
4'-Acetyl-3''-carbamoyl-[1,1':3',1''-terphenyl]-2-carboxylic acid


Acta Cryst. E69, o1596 (2013).

35) Ishikawa Y, Motohashi Y.
(E)-3-{[([1,1-Biphenyl]-3-ylmethyl)iminiumyl]methyl}-6,8-dichloro-2H-chromen-4-olate

Acta Cryst. E69, o1448 (2013).

34) Ishikawa Y, Motohashi Y.
6,8-Dichloro-4-oxochromene-3-carbaldehyde

Acta Cryst. E69, o1416 (2013).

33) Ishikawa Y, Matsuo S.
2-(Benzyloxy)isoquinoline-1,3(2H,4H)-dione

Acta Cryst. E69, o1311 (2013).

32) Ishikawa Y, Matsuo S.
2-Hydroxyisoquinoline-1,3(2H,4H)-dione

Acta Cryst. E69, o1312 (2013).

31) Ishikawa Y, Ugai A.
Ethyl (Z)-4-(4-ethoxy-1-hydroxy-3,4-dioxobut-1-en-1-yl)-[1,1-biphenyl]-3-carboxylate

Acta Cryst. E69, o1231 (2013).

30) Ishikawa Y, Motohashi Y.
(E)-6,8-Dichloro-3-{[(naphthalen-1-ylmethyl)iminiumyl]methyl}-2H-chromen-4-olate

Acta Cryst. E69, o1226 (2013).

29) Ishikawa Y, Motohashi Y.
3-[(E)-(Benzyliminiumyl)methyl]-6,8-dichloro-2H-chromen-4-olate

Acta Cryst. E69, o1225 (2013).

28) Ikawa T, Takagi A, Goto M, Aoyama Y, Ishikawa Y, Itoh Y, Fujii S, Tokiwa H, Akai S.
Regiocomplementary Cycloaddition Reactions of Boryl- and Silylbenzynes with 1,3-Dipoles: Selective Synthesis of Benzo-Fused Azole Derivatives.

J. Org. Chem., 78, 2965-2983 (2013).

27) Matsuno K, Yamazaki H, Isaka Y, Takai K, Unno Y, Ogo N, Ishikawa Y, Fujii S, Takikawa O, Asai A.
Novel candesartan derivatives as indoleamine 2,3-dioxygenase inhibitors.

Med. Chem. Commun., 3, 475-479 (2012).

26) Ishikawa Y, Fujii S.
Binding mode prediction and inhibitor design of anti-influenza virus diketo acids targeting metalloenzyme RNA polymerase by molecular docking.

Bioinformation, 6, 221-225 (2011).

25) Ikawa T, Nishiyama T, Shigeta T, Mohri S, Morita S, Takayanagi S, Terauchi Y, Morikawa Y, Takagi A, Ishikawa Y, Fujii S, Kita Y, Akai S.
ortho-Selective Nucleophilic Addition of Primary Amines to Silylbenzynes: Synthesis of 2-Silylanilines.

Angew. Chem. Int. Ed. 50, 5674–5677 (2011).

24) Ishikawa Y, Yamashita T, Fujii S, Uno T.
1,1’,1’’,1’’’-[Porphyrin-5,10,15,20-tetrayltetrakis(3,1-phenylenemethylene)]tetraquinolinium Tetrabromide.

Molbank, M704 (2010).

23) Ishikawa Y, Yamashita T, Fujii S, Uno T.
Zinc(II)-5,10,15,20-tetrakis(α-pyridino-m-tolyl)porphyrin Tetrabromide.

Molbank, M637 (2009).

22) Ishikawa Y, Yamakawa N, Uno T.
Binding of Cationic Bis-porphyrins Linked with p- or m- Xylylenediamine and Their Zinc(II) Complexes to Duplex DNA.

Molecules, 13, 3117-3128 (2008).

21) Ishikawa Y, Fujii S.
Molecular docking study of binding of TMPyP4 to a bimolecular human telomeric G-quadruplex.

Nucleic Acids Symp. Ser., 52, 173-174 (2008).

20) Ishikawa Y, Higashi E, Morioka H.
Molecular Docking of porphyrins with cationic limbs on Intramolecular G-quadruplex

Nucleic Acids Symp. Ser.,51, 247-248 (2007).

19) Ishikawa Y, Yamakawa N, Uno T.
Synthetic Control of Interchromophoric Interaction in Cationic Bis-porphyrins toward Efficient DNA Photocleavage with Singlet Oxygen Production in Aqueous Solution

Bioorg. Med. Chem.,15. 5230-5238 (2007).

18) Ishikawa Y, Tomisugi Y, Uno T.
Molecular modeling of Anti-parallel G-quadruplex DNA/TMPyP Complexes.

Nucleic Acids Symp.Ser. 50, 331-332 (2006).

17) Yamashita T, Uno T, Ishikawa Y.
Stabilization of Guanine Quadruplex DNA by the Binding of Porphyrins with Cationic Side Arms.

Bioorg. Med. Chem. 13, 2423-2430 (2005).

16) Kurosaki H, Ishikawa Y, Ishihara T, Yamamoto T, Yamaguchi Y, Goto M.
Mechanism of Formation of Iron(II) Complexes with Pentadentate Ligands via C-C Bond Formation between trans-[Fe(2,4-bis(2-pyridylmethylimino)pentane)(MeCN)2][ClO4]2・MeCN and Various Nitriles and Their Kinetic Fluctuation in Solution

Dalton Trans. 1086-1092 (2005).

15) Yamashita T, Hoashi Y, Tomisugi Y, Ishikawa Y, Uno T.
The C-Helix in CooA Rolls upon CO Binding to Ferrous Heme

J. Biol. Chem. 279, 47320-47325 (2004).

14) Yamashita T, Hoashi Y, Watanabe K, Tomisugi Y, Ishikawa Y, Uno T.
Roles of Heme Axial Ligands in the Regulation of CO Binding to CooA

J. Biol. Chem. 279, 21394-21400 (2004).

13) Uno T, Ryu D, Tsutsumi H, Tomisugi Y, Ishikawa Y, Wilkinson AJ, Sato H, Hayashi T.
Residues in the Distal Heme Pocket of Neuroglobin: Implications for the Multiple Ligand Binding Steps

J. Biol. Chem. 279, 5886-5893 (2004).

12) Kurosaki H, Ishikawa Y, Yamamoto T, Yamaguchi Y, Goto M.
Crystal Structure of a Copper(II) Complex of N-Anthracen-9-ylmethyl-N,N',N'-tris-pyridin-2-ylmethylethane-1,2-diamine

Anal. Sci. X-ray Struct. Anal. Online, 20, x93-x94 (2004).

11) Uno T, Sakamoto R, Tomisugi Y, Ishikawa Y, Wilkinson AJ.
Inversion of Axial Coordination in Myoglobin to Create a "Proximal" Ligand Binding Pocket

Biochemistry, 42, 10191-10199 (2003).

10) Aoki K, Ishikawa Y, Oyama M, Tomisugi Y, Uno T.
Self-Aggregation Inhibits the Photonuclease Activity of Porphyrins

Chem. Pharm. Bull. 51, 899-903 (2003).

9) Riordan CG, Krishnan R, Ishikawa Y.
Modeling the acetyl coenzyme A synthase active site

J. Inorg. Biochem. 96, 22 (2003).

8) Uno T, Aoki K, Shikimi T, Hiranuma Y, Tomisugi Y, Ishikawa Y.
Copper Insertion Facilitates Water-Soluble Porphyrin Binding to rA·rU and rA·dT Base Pairs in Duplex RNA and RNA·DNA Hybrids

Biochemistry 41, 13059-13066 (2002).

7) Ishikawa Y, Yamakawa N, Uno T.
Potent DNA Photocleavage by Zinc(II) Complexes of Cationic Bis-porphyrins Linked with Aliphatic Diamine

Bioorg. Med. Chem. 10, 1953-1960 (2002).

6) Kurosaki H, Maruyama A, Koike H, Kuroda N, Ishikawa Y, Goto M.
DNA cleavage by pentadentate iron(II) complexes containing fluoro-substituted phenyl groups

Bioorg. Med. Chem. Lett. 12, 201-203 (2002).

5) Yamakawa N, Ishikawa Y, Uno T.
Solution Properties and Photonuclease Activity of Cationic Bis-porphyrins Linked with a Series of Aliphatic Diamines

Chem. Pharm. Bull. 49, 1531-1540 (2001).

4) Uno T, Yukinari A, Tomisugi Y, Ishikawa Y, Makino R, Brannigan JA, Wilkinson AJ.
Cysteine Thiolate Coordination in the Ferrous CO Complex of an Engineered Cytochrome b562

J. Am. Chem. Soc. 123, 2458-2459 (2001).

3) Uno T, Yukinari A, Moriyama Y, Ishikawa Y, Tomisugi Y, Brannigan JA, Wilkinson AJ.
Engineering a Ligand Binding Pocket into a Four Helix Bundle Protein Cytochrome b562

J. Am. Chem. Soc. 123, 512-513 (2001).

2) Ishikawa Y, Yamashita A, Uno T.
Efficient Photocleavage of DNA by Cationic Porphyrin-acridine Hybrids with the Effective Length of Diamino Alkyl Chain

Chem. Pharm. Bull. 49, 287-293 (2001).

1) Ishikawa Y, Yamashita T, Tomisugi Y, Uno T.
Interaction of porphyrins bearing peripheral cationic heterocycles with G-quadruplex DNA

Nucleic Acids Symp. Ser. 1, 107-108 (2001).