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：　U065	報告日：　2010/07/23	所属：　東京大学医科学研究所	アッセイ者名：　古川　洋一	アッセイ名：　Tcf4活性阻害剤スクリーニング
概要大腸癌や肝癌においては、APCやβ-catenin、Axin1などの遺伝子異常により、転写因子TCF4の転写活性化が認められている。しかもこの活性化が大腸癌細胞の増殖およびstemnessの維持に重要である。そこでキナーゼインヒビターを含む既知の阻害薬が、TCF4転写活性を制御するかどうかを検討した。TCF4結合配列を持つTOP-Flash ルシフェラーゼレポータープラスミドまたはそのコントロールプラスミドを大腸癌細胞株などに導入し、レポーターアッセイを行った。この実験結果を通じて、既知の阻害薬の新しい作用の発見や、新しいWNTシグナル経路を調節するシグナルの発見など、有益な情報が得られるものと思われる。
評価のクライテリア toxicity: pGL-CONT 70%<control activity (solvent) non-specific: FOP 50%< control activity (solvent)
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：　2013/11/15

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．）

Well	KIT 1		KIT 2		KIT 3
Well	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	non-specific	Amastatin		Aurora kinase/cdk inhibitor
2 - B	Flutamide		Actinonin		Aurora kinase inhibitor II
2 - C	Daunorubicin, HCl	toxicity	Oligomycin		Aurora kinase inhibitor III
2 - D	Doxorubicin, HCl	non-specific	Bafilomycin A1		AG957
2 - E	Tamoxifen, citrate	non-specific	HA 14-1		LFM-A13
2 - F	Actinomycin D	non-specific	BH3I-1	toxicity	Terreic acid
2 - G	Camptothecin		LFM-A13		KN-93
2 - H	Aclarubicin		Terreic acid		KN-62
3 - A	Etoposide (VP-16)	toxicity	E-64d		Lavendustin C
3 - B	Cytochalasin D	non-specific	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	toxicity
4 - A	Kenpaullone	non-specific	AMD3100 octahydrochloride		Cdk4 inhibitor
4 - B	Purvalanol A	non-specific	NSC95397		NSC625987	non-specific
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	toxicity	Ellagic acid　(Dihydrate)
4 - H	NS-398		Sanguinarine	toxicity	TBB
5 - A	Sodium salicylate	toxicity	Glibenclamide		DMAT
5 - B	Theophylline		Dequalinium	toxicity	D4476	non-specific
5 - C	Azacytidine		Diazoxide	toxicity	TG003
5 - D	Aphidicolin		Valinomycin	toxicity	Diacylglycerol kinase inhibitor II
5 - E	AG1478		Nigericin	toxicity	IC60211
5 - F	Genistein		Diltiazem	toxicity	TX-1918
5 - G	Manumycin A		Nifedipine	toxicity	BPIQ-Ⅱ
5 - H	FTI-276		Verapamil	toxicity	AG1478
6 - A	SU1498		PGP-4008		AG490
6 - B	GGTI-286		Fumitremorgin C	toxicity	SU4984
6 - C	Dexamethasone		A23187	toxicity	SU5402
6 - D	GSK-3 inhibitor II		Ionomycin	toxicity	Flt-3 Inhibitor
6 - E	Scriptaid		Thapsigargin	toxicity	cFMS Receptor Tyrosine Kinase Inhibitor
6 - F	Trichostatin A		t-Butylhydroquinone (BHQ)		SU6656
6 - G	AG825		N-phenylanthranilic acid	toxicity	GSK-3 inhibitor IX
6 - H	Cycloheximide		DIDS	toxicity	1-Azakenpaullone
7 - A	Lovastatin		SB 218078	toxicity	Indirubin-3'-monoxime
7 - B	Radicicol		Debromohymenialdisine (DBH)	toxicity	AG825	non-specific
7 - C	17-AAG		Rotenone	toxicity	AG1024
7 - D	AG1024		Antimycin A1	toxicity	AGL 2263
7 - E	1400W, HCl		Leptomycin B*		BMS-345541	non-specific
7 - F	AMT, HCl		R59022		IKK-2 inhibitor VI	non-specific
7 - G	AG490		Dioctanoylglycol		IRAK-1/4 inhibitor	non-specific
7 - H	Cucurbitacin I	non-specific	RHC80267	toxicity	JAK Inhibitor I
8 - A	SP600125		Xanthohumol		JAK3 Inhibitor VI
8 - B	Damnacanthal		C75	toxicity	SP600125
8 - C	PD 98059		Cerulenin	toxicity	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	non-specific	Anacardic acid		MEK inhibitor I
9 - B	PD169316	toxicity	Chetomin		SU11274
9 - C	SB 203580	non-specific	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	non-specific	Baicalein		PDGF receptor tyrosine kinase inhibitor V
10 - A	Ro-20-1724		Nutlin-3	toxicity	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	non-specific	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	non-specific	Clofibrate		Y-27632
11 - G	FK-506	non-specific	BADGE		radicicol
11 - H	MG-132	non-specific	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	non-specific
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