Pat
J-GLOBAL ID：201303051540850803

遺伝子発現プロファイルを用いた漢方薬の評価法

Inventor：
木山 亮一

About 木山 亮一

, 
董 四君

About 董 四君


Applicant, Patent owner：
独立行政法人産業技術総合研究所

About 独立行政法人産業技術総合研究所


Gazette classification：特許公報
Application number (International application number)：2006151189
Publication number (International publication number)：2007319051
Patent number：5126644
Application date： May. 31, 2006
Publication date： Dec. 13, 2007
Claim (excerpt)：
【請求項1】 エストロゲン様活性を有する漢方薬(漢方生薬を含む)の活性成分の有効活性を評価する方法であって、 当該方法が、評価の際に用いるエストロゲン応答遺伝子を、以下1.〜115.に示す115個のエストロゲン応答遺伝子から選択して複数の機能別グループにグループ分けし、被検対象それぞれに機能別グループごとに少なくとも10個以上のエストロゲン応答遺伝子の発現プロファイルを作成し、被検対象間での機能別グループごとの相同性の統計的有意性を判定することで、エストロゲン活性を評価する方法であり、 前記漢方薬を生体に適用した場合に得られる機能別グループごとのエストロゲン応答遺伝子の発現プロファイルと、エストロゲンを生体に適用した場合に得られる機能別グループごとのエストロゲン応答遺伝子の発現プロファイルとを、機能別グループごとに比較して両者間の相同性の統計的有意性を判定する工程、及び 前記評価しようとする漢方薬の活性成分を生体に適用した場合に得られる機能別グループごとのエストロゲン応答遺伝子の発現プロファイルと前記漢方薬における前記機能別グループごとのエストロゲン応答遺伝子の発現プロファイルとを、機能別グループごとに比較して両者間の相同性の統計的有意性を判定する工程を含むことを特徴とする、前記方法; 1.phosphoenolpyruvate carboxykinase 2 (mitochondrial) (PCK2)[NM_004563] 2.phosphoserine aminotransferase 1 (PSAT1)[NM_058179] 3.asparagine synthetase (ASNS)[NM_133436] 4.phosphoglycerate dehydrogenase (PHGDH)[NM_006623] 5.serine hydroxymethyltransferase 2 (mitochondrial) (SHMT2)[NM_005412] 6.24-dehydrocholesterol reductase (DHCR24)[NM_014762] 7.tryptophanyl-tRNA synthetase (WARS) [NM_004184] 8.fucosyltransferase 8 (alpha (1,6) fucosyltransferase) (FUT8) [NM_178155] 9.argininosuccinate synthetase (ASS) [NM_054012] 10.enolase 2 (gamma, neuronal) (ENO2) [NM_001975] 11.enolase 3 (beta, muscle) (ENO3) [NM_001976] 12.fructose-1,6-bisphosphatase 1 (FBP1) [NM_000507] 13.methylenetetrahydrofolate dehydrogenase (NADP+dependent) 2, methenyl tetrahydrofolate cyclohydrolase (MTHFD2) [NM_006636] 14.carnitine palmitoyltransferase 1A (liver) (CPT1A) [NM_001876] 15.peptidase (mitochondrial processing) alpha (PMPCA) [NM_015160] 16.cathepsin D (lysosomal aspartyl peptidase) (CTSD) [NM_001909] 17.glutamic-oxaloacetic transaminase 1, soluble (aspartate aminotransferase 1) (GOT1) [NM_002079] 18.sorbitol dehydrogenase (SORD) [NM_003104] 19.stearoyl-CoA desaturase (delta-9-desaturase) (SCD) [NM_005063] 20.surfactant, pulmonary-associated protein B (SFTPB) [NM_000542] 21.serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 3 (SERPINA3) [NM_001085] 22.aconitase 2, mitochondrial (ACO2) [NM_001098] 23.glutamine-fructose-6-phosphate transaminase 1 (GFPT1) [NM_002056] 24.CDP-diacylglycerol-inositol 3-phosphatidyltransferase (phosphatidylinositol synthase) (CDIPT) [NM_006319] 25.ribosomal protein S6 kinase, 90kDa, polypeptide 3 (RPS6KA3) [NM_004586 ] 26.protein kinase C, delta (PRKCD) [NM_006254] 27.unc-51-like kinase 1 (C.elegans) (ULK1) [NM_003565] 28.integrin-linked kinase (ILK) [NM_004517]29.protein kinase C substrate 80K-H (PRKCSH) [NM_002743] 30.cyclin-dependent kinase inhibitor 1A (p21, Cip1) (CDKN1A) [NM_000389] 31.phosphoinositide-3-kinase, class 3 (PIK3C3) [NM_002647] 32.poliovirus receptor (PVR) [NM_006505] 33.progesterone receptor (PGR) [NM_000926] 34.insulin-like growth factor binding protein 5 (IGFBP5) [NM_000599] 35.catenin (cadherin-associated protein), delta 2 (neural plakophilin-related arm-repeat protein) (CTNND2) [NM_001332] 36.neuropeptide Y receptor Y1 (NPY1R) [NM_000909] 37.protein tyrosine phosphatase, non-receptor type 18 (brain-derived) (PTPN18) [NM_014369] 38.Rho GDP dissociation inhibitor (GDI) alpha (ARHGDIA) [NM_004309] 39.endothelin 2 (EDN2) [NM_001956] 40.stanniocalcin 2 (STC2) [NM_003714] 41.lectin, galactoside-binding, soluble, 3 binding protein (LGALS3BP) [NM_005567] 42.angiotensin II receptor, type 1 (AGTR1) [NM_000685] 43.proprotein convertase subtilisin/kexin type 6 (PCSK6) [NM_002570] 44.SH3-domain binding protein 5 (BTK-associated) (SH3BP5) [NM_004844] 45.growth differentiation factor 15 (GDF15) [NM_004864] 46.ras homolog gene family, member C (RHOC) [NM_175744] 47.estrogen receptor 1 (ESR1) [NM_000125] 48.trefoil factor 1 (breast cancer, estrogen-inducible sequence expressed in) (TFF1) [NM_003225] 49.aryl-hydrocarbon receptor nuclear translocator 2 (ARNT2) [NM_014862] 50.v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) (ERBB2) [NM_004448] 51.tribbles homolog 3 (Drosophila) (TRIB3) [NM_021158] 52.tyrosyl-tRNA synthetase (YARS) [NM_003680] 53.quiescin Q6 (QSCN6) [NM_002826] 54.cyclin A1 (CCNA1) [NM_003914] 55.interferon-related developmental regulator 1 (IFRD1) [NM_001550] 56.matrix Gla protein (MGP) [NM_000900] 57.amphiregulin (schwannoma-derived growth factor) (AREG) [NM_001657] 58.insulin-like growth factor binding protein 4 (IGFBP4) [NM_001552] 59.Kruppel-like factor 10 (KLF10) [NM_005655] 60.calpain, small subunit 1 (CAPNS1) [NM_001749] 61.interferon stimulated exonuclease gene 20kDa (ISG20) [NM_002201] 62.tumor-associated calcium signal transducer 2 (TACSTD2) [NM_002353] 63.PDZ domain containing 1 (PDZK1) [NM_002614] 64.ferritin, heavy polypeptide 1 (FTH1) [NM_002032] 65.peripheral myelin protein 22 (PMP22) [NM_000304] 66.lysosomal-associated membrane protein 3 (LAMP3) [NM_014398] 67.tumor protein p53 inducible protein 11 (TP53I11) [NM_006034] 68.tetraspanin 1 (TSPAN1) [NM_005727] 69.CCAAT/enhancer binding protein (C/EBP), beta (CEBPB) [NM_005194] 70.activating transcription factor 3 (ATF3) [NM_001674] 71.enolase 1, (alpha) (ENO1) [NM_001428] 72.activating transcription factor 3 (ATF3) [NM_004024] 73.early growth response 3 (EGR3) [NM_004430] 74.runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene) (RUNX1) [NM_001001890] 75.v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS) [NM_005252] 76.nuclear receptor interacting protein 1 (NRIP1) [NM_003489] 77.transcription elongation factor A (SII), 1 (TCEA1) [NM_006756] 78.general transcription factor II, i (GTF2I) [NM_032999] 79.TAF9 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 32kDa (TAF9) [NM_003187] 80.EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) [NM_004105] 81.reticulocalbin 1, EF-hand calcium binding domain (RCN1) [NM_002901] 82.cadherin 18, type 2 (CDH18) [NM_004934] 83.S100 calcium binding protein P (S100P) [NM_005980] 84.chromosome 1 open reading frame 19 (C1orf19) [NM_052965] 85.IMP4, U3 small nucleolar ribonucleoprotein, homolog (yeast) (IMP4) [NM_033416] 86.elongation factor Tu GTP binding domain containing 2 (EFTUD2)(U5-116KD) [NM_004247] 87.glycyl-tRNA synthetase (GARS) [NM_002047] 88.eukaryotic translation initiation factor 3, subunit 9 eta, 116kDa (EIF3S9) [NM_003751] 89.solute carrier family 12 (sodium/potassium/chloride transporters), member 2 (SLC12A2) [NM_001046] 90.solute carrier family 7 (cationic amino acid transporter, y+ system), member 5 (SLC7A5) [NM_003486] 91.solute carrier family 1 (glutamate/neutral amino acid transporter), member 4 (SLC1A4) [NM_003038] 92.solute carrier family 7, (cationic amino acid transporter, y+ system) member 11 (SLC7A11) [NM_014331] 93.lipocalin 2 (oncogene 24p3) (LCN2) [NM_005564] 94.exportin, tRNA (nuclear export receptor for tRNAs) (XPOT) [NM_007235] 95.solute carrier family 1 (neutral amino acid transporter), member 5 (SLC1A5) [NM_005628] 96.chloride intracellular channel 4 (CLIC4) [NM_013943] 97.transcobalamin I (vitamin B12 binding protein, R binder family) (TCN1) [NM_0 01062] 98.synaptogyrin 2 (SYNGR2) [NM_004710] 99.transmembrane 4 L six family member 1 (TM4SF1) [NM_014220] 100.heat shock 70kDa protein 1A (HSPA1A) [NM_005345] 101.heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa) (HSPA5) [NM_005347] 102.heat shock protein 90kDa beta (Grp94), member 1 (HSP90B1) (TRA1)[ NM_003299] 103.chromobox homolog 1 (HP1 beta homolog Drosophila) (CBX1) [NM_006807] 104.H3 histone, family 3B (H3.3B) (H3F3B) [NM_005324] 105.retinoblastoma binding protein 8 (RBBP8) [NM_002894] 106.tumor protein D52-like 1 (TPD52L1) [NM_003287] 107.absent in melanoma 1 (AIM1) [NM_001624] 108.chromosome 19 open reading frame 21 (C19orf21) [NM_173481] 109.SH3 domain binding glutamic acid-rich protein (SH3BGR) [NM_007341] 110.selenium binding protein 1 (SELENBP1) [NM_003944] 111.KIAA0196 (KIAA0196) [NM_014846] 112.LOC401397 [BC065765] 113.phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) [NM_021127] 114.PREDICTED: paternally expressed 10 (PEG10) [XM_496907] 115.DAZ associated protein 2 (DAZAP2) [NM_014764]。
IPC (8)：
C12Q 1/68 ( 200 6.01) ,  C12Q 1/02 ( 200 6.01) ,  C12N 15/09 ( 200 6.01) ,  C12M 1/00 ( 200 6.01) ,  G01N 33/15 ( 200 6.01) ,  G01N 33/50 ( 200 6.01) ,  G01N 33/53 ( 200 6.01) ,  G01N 37/00 ( 200 6.01)
FI (9)：
C12Q 1/68 ZNA A ,  C12Q 1/02 ,  C12N 15/00 A ,  C12N 15/00 F ,  C12M 1/00 A ,  G01N 33/15 Z ,  G01N 33/50 Z ,  G01N 33/53 M ,  G01N 37/00 102
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