化学療法基盤支援活動及びユーザによる評価結果




アッセイの概要
アッセイID: B151報告日: -所属: 化学療法基盤支援活動アッセイ者名: 深澤秀輔アッセイ名: プロテインキナーゼ阻害の検定 II-1
概要
チロシンキナーゼおよびその下流のシグナル伝達系は,多くのがん細胞で活性化しており,抗がん剤の有力な分子標的である.ここでは細胞を血小板由来増殖因子(platelet-derived growth factor, PDGF) 刺激して,活性化されるPDGFレセプターチロシンキナーゼおよびその下流の主要な細胞内シグナル伝達経路に対する検体の阻害効果を評価するとともに,4種類のチロシンキナーゼに対する阻害効果をcell based ELISAを用いて評価する. 実験系1:細胞内シグナル伝達 NRK細胞を96ウェルプレートにまき込み,3日間培養後,サンプルを添加,3時間処理した後にPDGFで刺激する.電気泳動用サンプルを調製し,リン酸化されたシグナル伝達分子(AKT,ERK,PKD,PLCγ1,S6 ribosomal protein)及びphosphotyrosineに対する抗体によるウェスタンブロットを行い,PDGFレセプターからの細胞内シグナル伝達に対する影響を評価する.
評価のクライテリア
10 μMで50%以上の阻害活性が認められたものを有効とする.+++, 1?M; ++, 10 ?M で50%以上の阻害
発表論文
レポート提出者によるレポート内容の最終確認日: -


評価結果の詳細(評価のクライテリアに基づいて陽性と判断された化合物については背景色を黄色にしています.)
WellKIT 1KIT 2KIT 3
compound結果compound結果compound結果
1 - Anone (DMSO)  none (DMSO)  none (DMSO) 
1 - B5-FU-  Pifithrin-a (cyclic)-  ABT-702- 
1 - CBestatin Hydrochloride-  PRIMA-1-  Akt Inhibitor IV- 
1 - DBleomycin sulfate-  Finasteride-  Akt Inhibitor VIII, Isozyme-Selective, Akti-1/2AKT++ 
1 - ECisplatin-  Aminoglutethimide-  Akt Inhibitor XI- 
1 - FMethotrexate-  Formestane-  compound CAKT++, ERK++, PKD++, S6R++, phosphotyrosine++ 
1 - GMitomycin C-  Mifepristone-  ATM/ATR kinase inhibitor- 
1 - HVinblastine sulfatephosphotyrosine ++  TOFA-  ATM kinase inhibitor- 
2 - APaclitaxel-  Amastatin-  Aurora kinase/cdk inhibitor- 
2 - BFlutamide-  Actinonin-  Aurora kinase inhibitor II- 
2 - CDaunorubicin, HClERK ++, phosphotyrosine ++  Oligomycin-  Aurora kinase inhibitor III- 
2 - DDoxorubicin, HClERK ++, phosphotyrosine ++  Bafilomycin A1ERK++, S6R++  AG957- 
2 - ETamoxifen, citrate-  HA 14-1-  LFM-A13- 
2 - FActinomycin D-  BH3I-1-  Terreic acid- 
2 - GCamptothecin-  LFM-A13-  KN-93- 
2 - HAclarubicin-  Terreic acid-  KN-62- 
3 - AEtoposide (VP-16)-  E-64d-  Lavendustin C- 
3 - BCytochalasin DAKT++, ERK ++, PKD ++, PLCγ1 ++, S6R ++, phosphotyrosine ++  ALLN-  Kenpaullone- 
3 - C2',5'-dideoxyadenosine-  CA-074-  purvalanol A- 
3 - DAKT inhibitor-  Pepstatin A-  Olomoucine- 
3 - ENL-71-101  Z-GLF-CMKAKT++, ERK++, PKD++, PLCγ1++, S6R++, phosphotyrosine++  Alsterpaullone, 2-cyanoethyl- 
3 - FAG957-  RS 102895-  Cdk1/2 inhibitor IIIPKD++, PLCγ1++, phosphotyrosine++ 
3 - GKN93-  SB 328437-  Cdk2/9 inhibitor- 
3 - HZ-VAD-FMK-  SB 225002-  NU6102- 
4 - AKenpaullone-  AMD3100 octahydrochloride-  Cdk4 inhibitorAKT++, ERK ++ 
4 - BPurvalanol A-  NSC95397AKT++, ERK++, PKD++, PLCγ1++, S6R++  NSC625987- 
4 - C3-ATA-  SC-ααδ9-  SB218078AKT++, ERK++, PKD++, PLCγ1++, S6R++, phosphotyrosine++ 
4 - DOlomoucine-  Amiloride-  isogranulatimide- 
4 - ETBB-  Lidocaine-  Chk2 inhibitor- 
4 - FSulindac sulfide-  Monensin-  Chk2 inhibitor II- 
4 - GValeryl salicylate-  Ouabain-  Ellagic acid (Dihydrate)- 
4 - HNS-398-  SanguinarineAKT++, ERK++, PKD++, S6R++, phosphotyrosine++  TBB- 
5 - ASodium salicylate -  Glibenclamide-  DMAT- 
5 - BTheophylline-  Dequalinium-  D4476- 
5 - CAzacytidine-  Diazoxide-  TG003- 
5 - DAphidicolin-  Valinomycin-  Diacylglycerol kinase inhibitor II- 
5 - EAG1478-  Nigericin-  IC60211- 
5 - FGenistein-  Diltiazem-  TX-1918- 
5 - GManumycin AAKT++, ERK++, PKD++, PLCγ1++, S6R++, phosphotyrosine++  Nifedipine-  BPIQ-Ⅱ- 
5 - HFTI-276-  Verapamil-  AG1478- 
6 - ASU1498-  PGP-4008-  AG490- 
6 - BGGTI-286-  Fumitremorgin C-  SU4984AKT++, ERK++, PKD++, PLCγ1++, phosphotyrosine++ 
6 - CDexamethasone-  A23187-  SU5402- 
6 - DGSK-3 inhibitor II-  IonomycinAKT++, ERK++, PKD++, PLCγ1++, S6R++, phosphotyrosine++  Flt-3 Inhibitor- 
6 - EScriptaid-  Thapsigargin-  cFMS Receptor Tyrosine Kinase Inhibitor- 
6 - FTrichostatin A-  t-Butylhydroquinone (BHQ)-  SU6656- 
6 - GAG825-  N-phenylanthranilic acid-  GSK-3 inhibitor IX- 
6 - HCycloheximide-  DIDS-  1-Azakenpaullone- 
7 - ALovastatin-  SB 218078PKD++, phosphotyrosine++  Indirubin-3'-monoxime- 
7 - BRadicicol-  Debromohymenialdisine (DBH)-  AG825- 
7 - C17-AAG-  Rotenone-  AG1024- 
7 - DAG1024-  Antimycin A1-  AGL 2263- 
7 - E1400W, HCl-  Leptomycin B*PKD++  BMS-345541- 
7 - FAMT, HCl-  R59022-  IKK-2 inhibitor VI- 
7 - GAG490-  Dioctanoylglycol-  IRAK-1/4 inhibitor- 
7 - HCucurbitacin IAKT+++, ERK+++, PKD+++, PLCγ1+++, S6R+++, phosphotyrosine+++  RHC80267-  JAK Inhibitor I- 
8 - ASP600125-  Xanthohumol-  JAK3 Inhibitor VIPKD++, PLCγ1++, phosphotyrosine++ 
8 - BDamnacanthal-  C75-  SP600125- 
8 - CPD 98059-  Cerulenin-  JNK inhibitor VIIIphosphotyrosine+++ 
8 - DU0126-  Tunicamycin-  Damnacanthal- 
8 - EFumagillin-  Deoxynojirimycin-  PP2- 
8 - FGM 6001-  Swainsonine-  ERK inhibitor II- 
8 - GN-Acetyl-L-cysteinephosphotyrosine++  LY 83583AKT++, ERK++, PKD++, PLCγ1++, S6R++, phosphotyrosine++  PD98059- 
8 - HAminoguanidine, HClphosphotyrosine++  ODQ-  U-0126- 
9 - AL-NMMA-  Anacardic acid-  MEK inhibitor I- 
9 - BPD169316-  ChetominAKT++, ERK++, PKD++, PLCγ1++, S6R++, phosphotyrosine++  SU11274- 
9 - CSB 203580-  Dimethyloxalylglycine-  ML-7- 
9 - DRapamycinphosphotyrosine++, S6R+++  HR22C16-  SB202190- 
9 - ENU1025-  Monastrol-  SB239063- 
9 - FBenzamide-  Nordihydroguaiaretic acid (NDGA)-  AG1296- 
9 - GD609-  ETYA-  SU11652AKT++, ERK++, PKD++, PLCγ1++, S6R++, phosphotyrosine++ 
9 - HIBMX-  Baicalein-  PDGF receptor tyrosine kinase inhibitor VAKT++, ERK+++, PKD +++, PLCγ1++, S6R++, phosphotyrosine+++ 
10 - ARo-20-1724-  Nutlin-3-  PDGF receptor tyrosine kinase inhibitor IVAKT++ 
10 - BZaprinast-  MDM2 inhibitor-  LY-294002AKT++ 
10 - CAG1296phosphotyrosine++  Phenelzine-  WortmanninAKT++ 
10 - DLY294002ATK++, S6R++  Deprenyl-  H-89- 
10 - EWortmanninATK++  Decylubiquinone-  4-cyano-3-methylisoquinoline- 
10 - FH-89, HCl-  Ro 5-4864-  Bisindolymaleimide I, HClPKD++ 
10 - GBisindolymaleimide I, HClphosphotyrosine++, PKD++, PLCγ1++  Lonidamine-  Go7874- 
10 - HH-7-  ML-7-  Rp-8-CPT-cGMPS- 
11 - AStaurosporineAKT+++, ERK+++, PKD+++, PLCγ1+++, S6R+++, phosphotyrosine+++  Benzylguanine-  KT5823- 
11 - BcPLA2inhibitor-  DFMO-  PKR inhibitorPLCγ1++ 
11 - COBAA-  KT 5823-  RAF1 kinase inhibitor IERK+++ 
11 - DCantharidin-  Rp-8-CPT-cGMPS-  ZM 336372PKD++, PKD++, phosphotyrosine++ 
11 - ECytostatin  MK 886-  H-1152- 
11 - FCyclosporin A-  Clofibrate-  Y-27632- 
11 - GFK-506-  BADGE-  radicicol- 
11 - HMG-132-  Troglitazone-  PP1 analog- 
12 - ALactacystin-  AZT-  Syk inhibitorERK ++ 
12 - BHydroxyurea-  Nalidixic acid-  SB431542ERK ++ 
12 - CHA1077-  a-Amanitin-  TGF-b RI kinase inhibitor IIERK ++ 
12 - DY27632-  MST-312-  Tpl2 kinase inhibitor- 
12 - EPP1 (analog)-  b-Rubromycinphosphotyrosine++  TrkA inhibitor- 
12 - FPP-H  SB 431542-  VEGFR receptor tyrosine kinase inhibitor IIAKT++, ERK+++, PK ++, PLCγ1++, S6R++, phosphotyrosine+++ 
12 - GNocodazole-  N1,N12-Diethylspermine (BESpm)-  VEGF recptor 2 kinase inhibitor I- 
12 - HDephostatin-  Fumonisin B1-  SU1498ERK++