GNF-5

製品コードS7526 バッチS752601

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₀H₁₇F₃N₄O₃
	分子量	418.37	CAS No.	778277-15-9
Solubility (25°C)*	体外	DMSO	83 mg/mL (198.38 mM)
		Ethanol	20 mg/mL warmed with 50ºC water bath (47.8 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	GNF-5 is a selective and allosteric Bcr-Abl inhibitor with IC50 of 220 nM.
in vitro	GNF-5, when used in combination with imatinib or nilotinib, suppresses the emergence of resistance mutations in vitro, and displays additive inhibitory activity in biochemical and cellular assays against Bcr-Abl T315I mutant. ^[1] GNF-5 shows potent antiproliferative activity with EC50 of 430 nM and 580 nM against wt-Bcr-Abl and E255K mutant Bcr-Abl transformed cells, respectively. ^[2]
in vivo	GNF-5 (100 mg/kg ) displays efficacy on wild-type and T315I Bcr-Abl dependent proliferation in xenograft and bone marrow transplantation models. Moreover, a combination of GNF-5 (75 mg/kg) with nilotinib (50 mg/kg) results in improved overall survival in a T315I Bcr-Abl BMT model. ^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	Kinetic characterization of Abl inhibition
キナーゼアッセイ	The ATP/NADH-coupled assay system in a 96-well format is used to determine the initial velocity of Abl tyrosine kinase catalyzed peptide phosphorylation. The reaction mixture contained 20 mM Tris-HCl, (pH 8.0), 50 mM NaCl, 10 mM MgCl₂, 2 mM PEP [2-(Phosphonooxy)- 2-propenoic acid) and 20 μg Abl peptide substrate (EAIYAAPFAKKK), fixed or varied (to determine inhibitor kinetic parameters) concentration of inhibitor applied, 1/50 of the final reaction mixture volume of PK/LDH enzyme (pyruvate kinase/lactic dehydrogenase enzymes from rabbit muscle), 160 μM NADH, 0.16 μM Abl, and ATP added last to start the reaction. Absorbance data are collected every 20s at 340 nm using a SpectraMax M5 Microplate Reader.
細胞アッセイ	細胞株	Ba/F3.p210 cells
	濃度	~10 μM
	反応時間	48 hours
	実験の流れ	Ba/F3.p210 cells are obtained by transfecting the IL-3-dependent murine hematopoietic Ba/F3 cell line with a pEYK vector containing p210BCR-ABL and Bcr-Abl mutations. All cell lines are cultured with 5% CO₂ at 37 °C in RPMI 1640 with 10% fetal bovine serum (FBS) and supplemented with 1% l-glutamine. Parental Ba/F3 cells are similarly cultured with 10% WEHI-conditioned medium as a source of IL-3. Transfected cell lines are cultured in media supplemented with 25 μg/mL zeocin. The 48 h cell proliferation studies are obtained using the CellTiter-Glo assay.
動物実験	動物モデル	Ba/F3.p210 xenograft mouse model
	投薬量	~100 mg/kg bid
	投与方法	p.o.

参考

カスタマーフィードバック

: Data from [Data independently produced by , , Leukemia, 2017, 31(5):1096-1107]

: Data from [Data independently produced by , , Oncotarget, 2017, 8(24):38717-38730]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Structural mechanism of a drug-binding process involving a large conformational change of the protein target [ Nat Commun, 2023, 14(1):1885]	PubMed: 37019905
Src stimulates Abl-dependent phosphorylation of the guanine exchange factor Net1A to promote its cytosolic localization and cell motility [ J Biol Chem, 2023, S0021-9258(23)01915-4]	PubMed: 37271338
Abl kinases can function as suppressors of tumor progression and metastasis [ Front Oncol, 2023, 13:1241056]	PubMed: 37746268
Abl kinases can function as suppressors of tumor progression and metastasis [ Front Oncol, 2023, 10.3389/fonc.2023.1241056]	PubMed: 37746268
Establishment and characterization of immortalized sweat gland myoepithelial cells [ Sci Rep, 2022, 12(1):7]	PubMed: 34997030
Imatinib can act as an Allosteric Activator of Abl Kinase [ J Mol Biol, 2021, 434(2):167349]	PubMed: 34774565
ABL1, Overexpressed in Hepatocellular Carcinomas, Regulates Expression of NOTCH1 and Promotes Development of Liver Tumors in Mice [ Gastroenterology, 2020, S0016-5085(20)30334-6]	PubMed: 32171747
Combating acquired resistance to MAPK inhibitors in melanoma by targeting Abl1/2-mediated reactivation of MEK/ERK/MYC signaling [ Nat Commun, 2020, 11(1):5463]	PubMed: 33122628
A novel human colon signet-ring cell carcinoma organoid line: establishment, characterization and application [ Carcinogenesis, 2020, 41(7):993-1004]	PubMed: 31740922
Abl and Arg mediate cysteine cathepsin secretion to facilitate melanoma invasion and metastasis [ Sci Signal, 2018, 11(518)eaao0422]	PubMed: 29463776

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人間や獣医の診断であるか治療的な使用のためにでない。

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