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：　B401	報告日：　-	所属：　化学療法基盤支援活動	アッセイ者名：　掛谷秀昭	アッセイ名：　低酸素誘導因子（HIF）阻害活性の評価
概要固形腫瘍内などの低酸素環境下に曝されている細胞の生存には、Hypoxia-inducible factor（HIF）が重要な役割を果たしている。そこで、HIFをターゲットとした分子標的治療には大きな期待が寄せられている。本測定系ではHIF-1/HIF-2のDNA結合配列(HRE; hypoxia response element)をルシフェラーゼ遺伝子の上流に挿入したプラスミドをレポーターとして用いたCell-based assayにより、提供化合物のHIFシグナル系に対する阻害効果を評価する。
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．
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．）

Well	KIT 1		KIT 2		KIT 3
Well	compound	結果	compound	結果	compound	結果
1 - A	none (DMSO)	Negative	none (DMSO)	Negative	none (DMSO)	Negative
1 - B	5-FU	Negative	Pifithrin-a (cyclic)	Positive	ABT-702	Positive
1 - C	Bestatin Hydrochloride	Negative	PRIMA-1	Negative	Akt Inhibitor IV	Positive
1 - D	Bleomycin sulfate	Negative	Finasteride	Negative	Akt Inhibitor VIII, Isozyme-Selective, Akti-1/2	Negative
1 - E	Cisplatin	Negative	Aminoglutethimide	Negative	Akt Inhibitor XI	Negative
1 - F	Methotrexate	Positive	Formestane	Negative	compound C	Positive
1 - G	Mitomycin C	Positive	Mifepristone	Negative	ATM/ATR kinase inhibitor	Negative
1 - H	Vinblastine sulfate	Positive	TOFA	Negative	ATM kinase inhibitor	Positive
2 - A	Paclitaxel	Negative	Amastatin	Negative	Aurora kinase/cdk inhibitor	Positive
2 - B	Flutamide	Negative	Actinonin	Negative	Aurora kinase inhibitor II	Negative
2 - C	Daunorubicin, HCl	Positive	Oligomycin	Negative	Aurora kinase inhibitor III	Negative
2 - D	Doxorubicin, HCl	Positive	Bafilomycin A1	Negative	AG957	Negative
2 - E	Tamoxifen, citrate	Negative	HA 14-1	Negative	LFM-A13	Negative
2 - F	Actinomycin D	Positive	BH3I-1	Negative	Terreic acid	Negative
2 - G	Camptothecin	Positive	LFM-A13	Negative	KN-93	Negative
2 - H	Aclarubicin	Negative	Terreic acid	Negative	KN-62	Negative
3 - A	Etoposide (VP-16)	Positive	E-64d	Negative	Lavendustin C	Negative
3 - B	Cytochalasin D	Negative	ALLN	Negative	Kenpaullone	Negative
3 - C	2',5'-dideoxyadenosine	Negative	CA-074	Negative	purvalanol A	Negative
3 - D	AKT inhibitor	Negative	Pepstatin A	Negative	Olomoucine	Negative
3 - E	NL-71-101	Negative	Z-GLF-CMK	Positive	Alsterpaullone, 2-cyanoethyl	Positive
3 - F	AG957	Negative	RS 102895	Negative	Cdk1/2 inhibitor III	Positive
3 - G	KN93	Negative	SB 328437	Negative	Cdk2/9 inhibitor	Positive
3 - H	Z-VAD-FMK	Negative	SB 225002	Negative	NU6102	Positive
4 - A	Kenpaullone	Negative	AMD3100 octahydrochloride	Negative	Cdk4 inhibitor	Negative
4 - B	Purvalanol A	Negative	NSC95397	Negative	NSC625987	Negative
4 - C	3-ATA	Negative	SC-ααδ9	Positive	SB218078	Negative
4 - D	Olomoucine	Negative	Amiloride	Negative	isogranulatimide	Negative
4 - E	TBB	Negative	Lidocaine	Negative	Chk2 inhibitor	Positive
4 - F	Sulindac sulfide	Negative	Monensin	Negative	Chk2 inhibitor II	Negative
4 - G	Valeryl salicylate	Negative	Ouabain	Positive	Ellagic acid　(Dihydrate)	Negative
4 - H	NS-398	Negative	Sanguinarine	Negative	TBB	Negative
5 - A	Sodium salicylate	Negative	Glibenclamide	Negative	DMAT	Negative
5 - B	Theophylline	Negative	Dequalinium	Positive	D4476	Negative
5 - C	Azacytidine	Negative	Diazoxide	Negative	TG003	Negative
5 - D	Aphidicolin	Negative	Valinomycin	Negative	Diacylglycerol kinase inhibitor II	Negative
5 - E	AG1478	Negative	Nigericin	Negative	IC60211	Negative
5 - F	Genistein	Negative	Diltiazem	Negative	TX-1918	Negative
5 - G	Manumycin A	Negative	Nifedipine	Negative	BPIQ-Ⅱ	Negative
5 - H	FTI-276	Negative	Verapamil	Negative	AG1478	Positive
6 - A	SU1498	Negative	PGP-4008	Negative	AG490	Negative
6 - B	GGTI-286	Negative	Fumitremorgin C	Negative	SU4984	Negative
6 - C	Dexamethasone	Negative	A23187	Negative	SU5402	Negative
6 - D	GSK-3 inhibitor II	Negative	Ionomycin	Negative	Flt-3 Inhibitor	Negative
6 - E	Scriptaid	Negative	Thapsigargin	Negative	cFMS Receptor Tyrosine Kinase Inhibitor	Negative
6 - F	Trichostatin A	Negative	t-Butylhydroquinone (BHQ)	Negative	SU6656	Negative
6 - G	AG825	Negative	N-phenylanthranilic acid	Negative	GSK-3 inhibitor IX	Positive
6 - H	Cycloheximide	Positive	DIDS	Negative	1-Azakenpaullone	Negative
7 - A	Lovastatin	Negative	SB 218078	Negative	Indirubin-3'-monoxime	Negative
7 - B	Radicicol	Positive	Debromohymenialdisine (DBH)	Negative	AG825	Negative
7 - C	17-AAG	Positive	Rotenone	Negative	AG1024	Negative
7 - D	AG1024	Negative	Antimycin A1	Negative	AGL 2263	Negative
7 - E	1400W, HCl	Negative	Leptomycin B*	Negative	BMS-345541	Negative
7 - F	AMT, HCl	Negative	R59022	Negative	IKK-2 inhibitor VI	Positive
7 - G	AG490	Negative	Dioctanoylglycol	Negative	IRAK-1/4 inhibitor	Positive
7 - H	Cucurbitacin I	Positive	RHC80267	Negative	JAK Inhibitor I	Positive
8 - A	SP600125	Negative	Xanthohumol	Negative	JAK3 Inhibitor VI	Positive
8 - B	Damnacanthal	Negative	C75	Negative	SP600125	Negative
8 - C	PD 98059	Negative	Cerulenin	Negative	JNK inhibitor VIII	Negative
8 - D	U0126	Negative	Tunicamycin	Negative	Damnacanthal	Negative
8 - E	Fumagillin	Negative	Deoxynojirimycin	Negative	PP2	Positive
8 - F	GM 6001	Negative	Swainsonine	Negative	ERK inhibitor II	Negative
8 - G	N-Acetyl-L-cysteine	Negative	LY 83583	Negative	PD98059	Negative
8 - H	Aminoguanidine, HCl	Negative	ODQ	Negative	U-0126	Negative
9 - A	L-NMMA	Negative	Anacardic acid	Negative	MEK inhibitor I	Negative
9 - B	PD169316	Negative	Chetomin	Negative	SU11274	Positive
9 - C	SB 203580	Negative	Dimethyloxalylglycine	Negative	ML-7	Negative
9 - D	Rapamycin	Negative	HR22C16	Negative	SB202190	Negative
9 - E	NU1025	Negative	Monastrol	Negative	SB239063	Positive
9 - F	Benzamide	Negative	Nordihydroguaiaretic acid (NDGA)	Negative	AG1296	Negative
9 - G	D609	Negative	ETYA	Negative	SU11652	Negative
9 - H	IBMX	Negative	Baicalein	Negative	PDGF receptor tyrosine kinase inhibitor V	Positive
10 - A	Ro-20-1724	Negative	Nutlin-3	Negative	PDGF receptor tyrosine kinase inhibitor IV	Positive
10 - B	Zaprinast	Negative	MDM2 inhibitor	Negative	LY-294002	Negative
10 - C	AG1296	Negative	Phenelzine	Negative	Wortmannin	Negative
10 - D	LY294002	Negative	Deprenyl	Negative	H-89	Negative
10 - E	Wortmannin	Negative	Decylubiquinone	Negative	4-cyano-3-methylisoquinoline	Negative
10 - F	H-89, HCl	Negative	Ro 5-4864	Negative	Bisindolymaleimide I, HCl	Negative
10 - G	Bisindolymaleimide I, HCl	Negative	Lonidamine	Negative	Go7874	Positive
10 - H	H-7	Negative	ML-7	Negative	Rp-8-CPT-cGMPS	Negative
11 - A	Staurosporine	Positive	Benzylguanine	Negative	KT5823	Negative
11 - B	cPLA2inhibitor	Negative	DFMO	Negative	PKR inhibitor	Positive
11 - C	OBAA	Negative	KT 5823	Negative	RAF1 kinase inhibitor I	Negative
11 - D	Cantharidin	Negative	Rp-8-CPT-cGMPS	Negative	ZM 336372	Negative
11 - E	Cytostatin	Negative	MK 886	Negative	H-1152	Negative
11 - F	Cyclosporin A	Negative	Clofibrate	Negative	Y-27632	Negative
11 - G	FK-506	Negative	BADGE	Negative	radicicol	Positive
11 - H	MG-132	Positive	Troglitazone	Negative	PP1 analog	Positive
12 - A	Lactacystin	Positive	AZT	Negative	Syk inhibitor	Positive
12 - B	Hydroxyurea	Negative	Nalidixic acid	Negative	SB431542	Negative
12 - C	HA1077	Negative	a-Amanitin	Positive	TGF-b RI kinase inhibitor II	Positive
12 - D	Y27632	Negative	MST-312	Negative	Tpl2 kinase inhibitor	Positive
12 - E	PP1 (analog)	Positive	b-Rubromycin	Negative	TrkA inhibitor	Negative
12 - F	PP-H	Negative	SB 431542	Positive	VEGFR receptor tyrosine kinase inhibitor II	Negative
12 - G	Nocodazole	Negative	N1,N12-Diethylspermine (BESpm)	Negative	VEGF recptor 2 kinase inhibitor I	Negative
12 - H	Dephostatin	Negative	Fumonisin B1	Negative	SU1498	Negative