アッセイID: B301 | 報告日: 2011/03/01 | 所属: 化学療法基盤支援活動 | アッセイ者名: 清宮啓之 | アッセイ名: アンドロゲン受容体シグナル阻害活性の検定 |
概要 前立腺がんの発生および生育は、男性ホルモンであるアンドロゲンとその受容体(androgen receptor, AR)を介した細胞内シグナル伝達に依存する。アンドロゲン産生阻害薬や抗アンドロゲン薬を用いた内分泌療法は、ARシグナル伝達を遮断することにより、すぐれた制がん効果を発揮する。しかしながら、これに耐性の予後不良がんが数年後に再発することが多く、根治療法の確立が急務とされている。再燃性前立腺がんでは、抗アンドロゲン薬で活性化してしまう変異型ARや、アンドロゲン非依存的なARシグナルが作動していることが多い。このように、前立腺がんの発生・進展・再燃のすべての段階にARシグナルが関与しており、従来の内分泌療法薬とは異なる、新たなARシグナル阻害薬の開発が望まれている。本系は、前立腺腫瘍マーカーであるPSA(prostate specific antigen)遺伝子のプロモーター活性を指標に、検体のARシグナル阻害活性を評価する。 |
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評価のクライテリア IC50値が0.2μM以下=「有効 (+++)」、0.2-2μM=「有効 (++)」、2-20μM=「やや有効 (+)」と判定する。 |
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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: - |
Well | KIT 1 | KIT 2 | KIT 3 | |||
compound | 結果 | compound | 結果 | compound | 結果 | |
1 - A | none (DMSO) | none (DMSO) | none (DMSO) | |||
1 - B | 5-FU | Pifithrin-a (cyclic) | ABT-702 | |||
1 - C | Bestatin Hydrochloride | PRIMA-1 | Akt Inhibitor IV | |||
1 - D | Bleomycin sulfate | Finasteride | Akt Inhibitor VIII, Isozyme-Selective, Akti-1/2 | |||
1 - E | Cisplatin | Aminoglutethimide | Akt Inhibitor XI | |||
1 - F | Methotrexate | Formestane | compound C | |||
1 - G | Mitomycin C | + | Mifepristone | ATM/ATR kinase inhibitor | + | |
1 - H | Vinblastine sulfate | ++ | TOFA | ATM kinase inhibitor | ||
2 - A | Paclitaxel | Amastatin | Aurora kinase/cdk inhibitor | |||
2 - B | Flutamide | Actinonin | Aurora kinase inhibitor II | |||
2 - C | Daunorubicin, HCl | Oligomycin | Aurora kinase inhibitor III | |||
2 - D | Doxorubicin, HCl | ++ | Bafilomycin A1 | +++ | AG957 | |
2 - E | Tamoxifen, citrate | HA 14-1 | LFM-A13 | |||
2 - F | Actinomycin D | +++ | BH3I-1 | Terreic acid | ||
2 - G | Camptothecin | +++ | LFM-A13 | KN-93 | + | |
2 - H | Aclarubicin | ++ | Terreic acid | KN-62 | ||
3 - A | Etoposide (VP-16) | E-64d | Lavendustin C | |||
3 - B | Cytochalasin D | ++ | ALLN | Kenpaullone | ||
3 - C | 2',5'-dideoxyadenosine | CA-074 | purvalanol A | |||
3 - D | AKT inhibitor | Pepstatin A | Olomoucine | |||
3 - E | NL-71-101 | Z-GLF-CMK | + | Alsterpaullone, 2-cyanoethyl | ||
3 - F | AG957 | RS 102895 | Cdk1/2 inhibitor III | |||
3 - G | KN93 | + | SB 328437 | Cdk2/9 inhibitor | ||
3 - H | Z-VAD-FMK | SB 225002 | NU6102 | |||
4 - A | Kenpaullone | AMD3100 octahydrochloride | Cdk4 inhibitor | |||
4 - B | Purvalanol A | NSC95397 | + | NSC625987 | ||
4 - C | 3-ATA | SC-ααδ9 | SB218078 | |||
4 - D | Olomoucine | Amiloride | isogranulatimide | |||
4 - E | TBB | Lidocaine | Chk2 inhibitor | |||
4 - F | Sulindac sulfide | Monensin | +++ | Chk2 inhibitor II | ||
4 - G | Valeryl salicylate | Ouabain | +++ | Ellagic acid (Dihydrate) | ||
4 - H | NS-398 | Sanguinarine | TBB | |||
5 - A | Sodium salicylate | Glibenclamide | DMAT | |||
5 - B | Theophylline | Dequalinium | D4476 | |||
5 - C | Azacytidine | ++ | Diazoxide | TG003 | ||
5 - D | Aphidicolin | Valinomycin | Diacylglycerol kinase inhibitor II | |||
5 - E | AG1478 | Nigericin | +++ | IC60211 | ||
5 - F | Genistein | Diltiazem | TX-1918 | |||
5 - G | Manumycin A | Nifedipine | BPIQ-Ⅱ | |||
5 - H | FTI-276 | Verapamil | AG1478 | |||
6 - A | SU1498 | + | PGP-4008 | AG490 | ||
6 - B | GGTI-286 | Fumitremorgin C | SU4984 | |||
6 - C | Dexamethasone | A23187 | ++ | SU5402 | ||
6 - D | GSK-3 inhibitor II | Ionomycin | + | Flt-3 Inhibitor | ||
6 - E | Scriptaid | Thapsigargin | +++ | cFMS Receptor Tyrosine Kinase Inhibitor | ||
6 - F | Trichostatin A | t-Butylhydroquinone (BHQ) | SU6656 | |||
6 - G | AG825 | N-phenylanthranilic acid | GSK-3 inhibitor IX | |||
6 - H | Cycloheximide | DIDS | 1-Azakenpaullone | |||
7 - A | Lovastatin | SB 218078 | Indirubin-3'-monoxime | |||
7 - B | Radicicol | Debromohymenialdisine (DBH) | AG825 | |||
7 - C | 17-AAG | ++ | Rotenone | AG1024 | ||
7 - D | AG1024 | Antimycin A1 | AGL 2263 | |||
7 - E | 1400W, HCl | ++ | Leptomycin B* | ++ | BMS-345541 | |
7 - F | AMT, HCl | R59022 | IKK-2 inhibitor VI | |||
7 - G | AG490 | Dioctanoylglycol | IRAK-1/4 inhibitor | |||
7 - H | Cucurbitacin I | ++ | RHC80267 | JAK Inhibitor I | ||
8 - A | SP600125 | Xanthohumol | + | JAK3 Inhibitor VI | ||
8 - B | Damnacanthal | C75 | SP600125 | |||
8 - C | PD 98059 | Cerulenin | JNK inhibitor VIII | |||
8 - D | U0126 | Tunicamycin | + | Damnacanthal | ||
8 - E | Fumagillin | Deoxynojirimycin | PP2 | |||
8 - F | GM 6001 | Swainsonine | ERK inhibitor II | |||
8 - G | N-Acetyl-L-cysteine | LY 83583 | PD98059 | |||
8 - H | Aminoguanidine, HCl | ODQ | U-0126 | |||
9 - A | L-NMMA | Anacardic acid | MEK inhibitor I | |||
9 - B | PD169316 | Chetomin | SU11274 | |||
9 - C | SB 203580 | Dimethyloxalylglycine | ML-7 | |||
9 - D | Rapamycin | HR22C16 | SB202190 | |||
9 - E | NU1025 | Monastrol | SB239063 | |||
9 - F | Benzamide | Nordihydroguaiaretic acid (NDGA) | AG1296 | |||
9 - G | D609 | ETYA | SU11652 | |||
9 - H | IBMX | Baicalein | PDGF receptor tyrosine kinase inhibitor V | |||
10 - A | Ro-20-1724 | Nutlin-3 | PDGF receptor tyrosine kinase inhibitor IV | |||
10 - B | Zaprinast | MDM2 inhibitor | LY-294002 | |||
10 - C | AG1296 | Phenelzine | Wortmannin | |||
10 - D | LY294002 | Deprenyl | H-89 | |||
10 - E | Wortmannin | Decylubiquinone | 4-cyano-3-methylisoquinoline | |||
10 - F | H-89, HCl | Ro 5-4864 | Bisindolymaleimide I, HCl | |||
10 - G | Bisindolymaleimide I, HCl | Lonidamine | Go7874 | |||
10 - H | H-7 | ML-7 | Rp-8-CPT-cGMPS | |||
11 - A | Staurosporine | +++ | Benzylguanine | KT5823 | ||
11 - B | cPLA2inhibitor | DFMO | PKR inhibitor | |||
11 - C | OBAA | KT 5823 | RAF1 kinase inhibitor I | |||
11 - D | Cantharidin | ++ | Rp-8-CPT-cGMPS | ZM 336372 | ||
11 - E | Cytostatin | + | MK 886 | H-1152 | ||
11 - F | Cyclosporin A | Clofibrate | Y-27632 | |||
11 - G | FK-506 | BADGE | radicicol | |||
11 - H | MG-132 | ++ | Troglitazone | PP1 analog | ||
12 - A | Lactacystin | + | AZT | Syk inhibitor | ||
12 - B | Hydroxyurea | Nalidixic acid | SB431542 | |||
12 - C | HA1077 | a-Amanitin | TGF-b RI kinase inhibitor II | |||
12 - D | Y27632 | MST-312 | Tpl2 kinase inhibitor | |||
12 - E | PP1 (analog) | b-Rubromycin | TrkA inhibitor | |||
12 - F | PP-H | SB 431542 | VEGFR receptor tyrosine kinase inhibitor II | |||
12 - G | Nocodazole | N1,N12-Diethylspermine (BESpm) | VEGF recptor 2 kinase inhibitor I | |||
12 - H | Dephostatin | Fumonisin B1 | SU1498 | + |