Ⅰ 新薬開発と安全性予測 - kpia.jp

1 75 I 76 18 Replacement Reduction Refinement Refinement Replacement 11 2007

2 17 6 R Replacement ( )Reduction ( )Refinement ( )* 2005 11 (JaCVAM*, ECVAM, ICCVAM) 77 Target Target benefit / risk)> 2 3 5 2 7 2 3 1974 Nialamide1982 Benoxaprofen1983 Zimeldine1985 1993 Moxisylyte1996 Chlormezanone 1979 Ticrynafen2000 Troglitazone1998 Bromfenac1999 Trovafloxacin 78

3 79 14 2002 18 2006 17 15 80 Affymetrix Gene Chip

4 15 TGP) TGP) 14 2002) 18 2006 2007 81 2007 Gene Chip 150 1,500 150 Affymetrix GeneChip DNA Spike RNA mRNA 2) 150 3) QC 4)

5 5) TGP TGP 82 10 11 10 in vivo 24 28 in vitro 11 Affymetrix Gene Chip TGP TGP 4 3,7,14,28 d 4 3,6,9,24 h 0 5 3 2,8,24 h 0 In vivo In vivo In vitro In vitro Affymetrix GeneChip Array30,000 mRNA 83 12 Array 12 13 37 150 14

6 TGP TGP 84 13 14 1357911131517192123252729313335373HC6HC9 HC24HC4DC8DC15DC29DC02004006008001000120 014001600 ThioacetamideMethapyrileneTNFRSF16 associated protein 1 TGP TGP ID 85 15 15 16 k-means

7 Prediction analysis of microarray (PAM), support vector machine (SVM) 86 16 17 17 18 TGP 87 18

8 19 CFB HiWY MidWY HiBBr MidBBr HiCFB MidASA HiGFZ MidGFZ Hi CYPoxydative stressglycolitic pathwayubiquitin pathwayTAAMPTAAMPTAAMPTAAMP kk--meansmeans CYP, 88 19 K-means 20

9 21 20 etc. 8